Protein compounds

ABSTRACT

The present invention is directed to certain multiprotein compounds and methods for using such compounds in the treatment of psoriasis, arthritis, erythropoietic protoporphyria, and scar tissue and wounds. These multiprotein compounds include beta-lactoglobulin, alpha-lactalbumin, and bacitracin. The beta-lactoglobulin proteins are linked to alpha-lactalbumin proteins by a plurality of organic linkages formed by reacting various alcohols, e.g., noncyclic alcohols, steroid alcohols, triterpenoid alcohols, and thioglycerol therewith. The alpha-lactalbumin proteins are linked to the bacitracin proteins by a plurality of organic linkages formed by reacting with fatty acids therewith. A selenium ion may be bonded to each bacitracin protein molecule of the multiprotein compounds. Additionally, pairs of bacitracin molecules may be linked by zinc ions or other cations, to form a salt with the bacitracin.

RELATED APPLICATIONS

This application is a continuation-in-part of my copending U.S. patentapplication Ser. No. 194,626, filed Oct. 6, 1980, (now abandoned)entitled "MATREX," which is incorporated herein by reference.

BACKGROUND Field of the Invention

The present invention relates to multiprotein compounds which areparticularly useful in the treatment of such medical disorders aspsoriasis, arthritis, erythropoietic protoporphyria, and scar tissue andwounds.

The Prior Art

A. Psoriasis

Psoriasis is a skin disease which is typically characterized by white orred scaly patches of skin at practically any body location. Ulcerationsof the skin and bleeding may also, but not necessarily, be experiencedby some victims of psoriasis. In extremely severe cases, bloodtransfusions may even be necessary. It is estimated that one to threepercent (1-3%) of the world population suffers from psoriasis.

Simply stated, psoriasis may be defined as an acute overproliferation ofcorneocytes (white skin cells). Typical psoriasis treatments have thusattempted to impede the proliferation of corneocytes and to allow theskin layers to heal themselves. Typical treatments include the followingcategories of medicants: (1) anti-infectives, (2) cleansing agents anddetergents, (3) enzyme preparations, (4) preparations containing tar,allantoin, or anthralin, and (5) preparations containing vitamins andnutrients.

The anti-infective treatments contain such active ingredients asfluocinolone acetonide, neomycin, and p-chloro-m-xylenol, generallyeither in a detergent base or in an oil-water emulsion. It has beenfound, however, that these treatments provide limited active absorptioninto the skin, and are extremely limited in their antiproliferativeaction against the corneocytes.

Cleansing agents and detergents are useful for washing away dead skincells; however, these are not particularly useful in stoppingproliferation of the corneocytes.

Typical enzyme preparations include such ingredients as pancreatin andpyridoxine hydrochloride. These preparations are generally taken orallyand attempt to disrupt the enzymatic reactions which occur during theproliferative cycles of the corneocytes. However, in reality, thesepreparations achieve only minimal disruption of the proliferative cyclesand are often absorbed or destroyed, in large part, before reaching thecorneocytes.

A typical hormone and steroid treatment of psoriasis is the injection ofcorticotrophin. Since many of the anti-infective treatments involvecortico-steroids, many of the same problems associated withanti-infective treatments are also characteristic of the hormone steroidtreatments.

The preparations containing tar, allantoin and anthralin are generallyapplied topically. The action of these preparations in slowing theproliferation of corneocytes has been found to be limited. Moreover,these preparations can result in many undesirable effects, e.g., skincancer, organ cancer, an increase in the aging process, conjunctivitis,corneal opacity of the eyes, renal and skin irritation, postularfolliculitis, cutaneous sensitization of the skin or scalp,poly-metastatitis, metastatic carcinoma, partial or total blindness, anddamage to or failure of the liver, bladder, or kidneys.

A typical vitamin and nutrient treatment includes as an activeingredient, 13-cis-retenoic acid (modified vitamin A). However, theactivity of such a preparation in treating psoriasis has been found tobe extremely limited.

From the foregoing, it will be appreciated that what is needed in theart is a psoriasis treatment which can be readily absorbed by the skinand which is effective in stopping the proliferation of corneocytes,without exhibiting adverse side effects. Such a compound and treatmentare disclosed and claimed herein.

B. Arthritis

Arthritis may be defined as an acute inflammation of the joints,generally accompanied by significant swelling and pain. In somearthritis victims, calcification of the joints and partial or totalimmobilization thereof may also occur. Arthritis is a well-known malady;indeed, it is estimated that every thirty-three (33) seconds, anotherAmerican is afflicted with arthritis. Arthritis is generally believed tobe caused by the polymerization of collagen in the joints.

Typical preparations for the treatment of arthritis have included thefollowing, and combinations thereof: (1) adenosine preparations, (2)anabolic agents, (3) analgesics, (4) anesthetics, (5) enzymes, (6)hormones and steroids, (7) hypnotics and tranquilizers, (8) musclerelaxants, (9) narcotics, and (10) phenylbutazones. These drugs,however, have been found to be extremely limited in their action ofbreaking up the polymerized collagen which causes arthritis and aregenerally directed more toward temporarily relieving the symptoms ofarthritis such as arthritic pain. Moreover, these drugs are accompaniedby numerous undesirable side effects.

Some of the side effects experienced with the use of the adenosinepreparations include flushing of the skin and face, restlessness,hypertension, dizziness, dyspnea, epigastric discomfort, nausea,erythema, and diuresis.

Side effects associated with the anabolic agents include deepening ofthe voice (in women), sterility (primarily in men and children),carcinoma of the prostate gland, arteriosclerosis, hypertensive heartdisease, periodic paralysis, and many of the side effects previouslylisted for the cancer hormone and steroid treatments.

Side effects sometimes associated with the analgesics include nausea,vomiting, intestinal irritation, bleeding of the stomach, thinning ofthe blood, kidney damage, and addiction. Gastrointestinal upset is alsoa common side effect experienced with the use of the enzymepreparations. The side effects experienced with the arthritis hormoneand steroid preparations are similar to those experienced with thehormone and steroid preparations for the treatment of cancer. Sideeffects associated with hypnotics and tranquilizers include thewell-known toxicities of barbiturates, hypersensitivity, and addiction.

Those side effects associated with the muscle relaxants includedelerium, confusion, constipation, depression, hiccups, hypoactivity,hypertension, headaches, nausea, salivation, skin rash, slurried speech,tremors, urine retention, urticaria, hallucinations, muscle spasms,insomina, rage, jaundice, and addiction. The narcotic preparations alsohave undesirable side effects, including gastrointestinal problems,headaches, and addiction, while those associated with the phenylbutazonepreparations include fever, sore throats, lesions of the mouth,intestinal hemorrhaging, skin reactions, and an increase in weight.

It will thus be appreciated that what is needed in the art is aneffective treatment for arthritis which effectively breaks uppolymerized collagen, which prevents further polymerization of collagen,and which is not accompanied by undesirable side effects. Such acompound and treatment are disclosed and claimed herein.

C. Erythropoietic Protoporphyria

Erythropoietic protoporphyria is a disease which effects one in aboutevery 100,000 persons. It is characterized by a concentration ofporphyrin IX in the urine, and often by swelling, discoloration, andsplitting of the skin. Porphyrin IX, a precursor of hemoglobin,accumulates in the victims of this disease when the liver and red bonemarrow fail to properly manufacture hemoglobin.

Porphyrin IX reacts with the cell wall so as to cause an accumulation ofporphyrin just below the cell membrane, thus resulting in the swelling,discoloration, and splitting of the skin cells. Erythropoieticprotoporphyria may also be characterized by other symptoms such as braindisfunctions, individual idiosyncrasies, liver and kidney damage,ruptured veins and arteries, hemorrhaging at various body locations, andeven mental retardation in severe cases.

No compound or method exists in the prior art for curing or eveneffectively treating erythropoietic protoporphyria. It would, therefore,be a significant advancement in the art to provide an effectivetreatment for erythropoietic protoporphyria. Such a compound andtreatment are disclosed and claimed herein.

D. Scar Tissue and Wounds

Typical prior art preparations for treating scar tissue and woundsinclude: (1) anti-infectives, (2) enzymes and antioxidants, (3) hormonesand steroids, and (4) tissue stimulants. Most of these treatments haveundesirable side effects and are usually not effective in promotingactual tissue regeneration.

The anti-infective preparations attempt to reduce bacterial infection,thereby promoting wound healing. These preparations do little, ifanything, to actually activate the tissue regeneration mechanisms of thebody. Moreover, side effects such as skin irritations or sensitizationreactions may be experienced during the use of such preparations.

The enzyme and antioxidant preparations were developed with the goal ofactually activating the healing mechanisms of the body, therebypromoting tissue regeneration. However, in reality, their activity inpromoting tissue regeneration is extremely limited, if not nonexistant.Moreover, adverse side effects such as hemopillia, allergic reactions,nausea, vomiting, diarrhea, skin rash, and urticaria may be experiencedwith the use of such preparations.

The hormone and steroid preparations have a certain amount ofanti-inflammatory action and attempt to provide the scar tissue andwounds with some of the new materials needed in the construction of newcellular tissue. These preparations, however, only provide a few of theneeded raw materials and have many adverse side effects which arediscussed hereinabove in connection with the hormone and steroidtreatments used for cancer.

The tissue stimulant preparations are usually applied topically asbiological cleansers and contain proteins, amino acids, and/or vitaminswhich are needed for repairing cellular breaks in the tissues. Althoughthese preparations provide some of the raw materials for building newtissue, they do not provide all the necessary raw materials and do notin themselves promote tissue regeneration.

From the foregoing, it will be appreciated that it would be asignificant advancement in the art to provide a treatment for scartissue and wounds which has anti-bacterial activity; supplies most, ifnot all, of the raw materials necessary to promote wound healing;promotes actual tissue regeneration; and yet does not have any adverseside effects. Such a compound and treatment are disclosed and claimedherein.

BRIEF SUMMARY AND OBJECTS OF THE INVENTION

The present invention relates to multiprotein chemical compounds andmethods for treating cancer, psoriasis, arthritis, erythropoieticprotoporphyria, and scar tissue and wounds. The various chemicalcompounds used in these treatments are substantially similar and includebeta-lactoglobulin, alpha-lactalbumin, and bactitracin. Thealpha-lactalbumin molecules are linked to the beta-lactoglobulinmolecules by a plurality of organic linkages which are formed byreacting alcohols therewith; the alcohols are selected from the groupconsisting of noncyclic aliphatic alcohols, steroid alcohols, andtriterpenoid alcohols. Additionally, thioglycerol molecules may bereacted with the beta-lactoglobulin molecules and the alpha-lactalbuminmolecules to provide further organic linkages therebetween, thusproviding additional strength and stability to the overall chemicalstructure. The bacitracin molecules are linked to the alpha-lactalbuminmolecules by a plurality of organic linkages which are formed byreacting fatty acids therewith. Additionally, the compounds furtherinclude selenium ions, each ion having a +2 charge. Each selenium ion issubstituted for a sulfur atom in a sulfide bond between adjacentisoleucine and cysteine amino acid residues in a correspondingbacitracin molecule. Optionally, compounds within the scope of thepresent invention may further include four zinc ions, each ion having a+2 charge and being associated with two bacitracin molecules so as toform a zinc salt therewith.

In the treatment of the medical disorders discussed above, themultiprotein compounds of the present invention may be applied eithertopically or surgically, as in needed. Significantly, the multiproteincompounds of the present invention have not been found to have adverseside effects, and yet have exhibited: (1) antimitotic activity instopping the proliferation of cancerous cells without harming healthycells, (2) the ability to be readily absorbed by skin afflicted withpsoriasis and to stop proliferation of corneocytes, (3) activity inbreaking up polymerized collagen and in preventing furtherpolymerization of collagen for the effective treatment of arthritis, (4)activity in the effective treatment of erythropoietic protoporphyria,and (5) activity in the effective treatment of scar tissue and in thepromotion of wound healing and tissue regeneration.

It is, therefore, an object of the present invention to provide novelmultiprotein compounds which include beta-lactoglobulin,alpha-lactalbumin, and bacitracin.

It is another object of the present invention to provide a novelseleno-bacitracin compound which is made from bacitracin and seleniumions, each selenium ion being substituted for a sulfur atom in a sulfidebond between adjacent isoleucine and cysteine amino acid residues in acorresponding bacitracin molecule.

Still another object of the present invention is to provide an effectivemethod for prohibiting the replication of deoxyribonucleic acid incells, thereby prohibiting mitosis.

Yet another object of the present invention is to provide an effectivemethod for treating psoriasis by stopping proliferation of corneocytes.

A further object of the present invention is to provide an effectivemethod for treating arthritis.

Still another object of the present invention is to provide an effectivemethod for treating erythropoietic protoporphyria.

Yet another object of the present invention is to provide an effectivemethod for treating scar tissue and for promoting wound healing andtissue regeneration.

These and other objects and features of the present invention willbecome more fully apparent from the following description and appendedclaims, taken in conjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a representative schematic illustration of the novel compoundsof the present invention.

FIG. 2 is a schematic illustration of the manner in whichbeta-lactoglobulin molecules are linked to alpha-lactalbumin moleculesin the compounds of the present invention, and the manner in whichalpha-lactalbumin molecules are linked to bacitracin molecules.

FIGS. 3 A-D illustrate the various alcohols which are used to linkbeta-lactoglobulin molecules to alpha-lactalbumin molecules in thecompounds of the present invention. In particular, FIG. 3A illustrates anoncyclic aliphatic alcohol molecule; FIG. 3B illustrates a steroidalcohol molecule; FIG. 3C illustrates a triterpenoid alcohol molecule;and FIG. 3D illustrates a thioglycerol molecule.

FIG. 4 illustrates the fatty acids which are used to linkalpha-lactalbumin molecules to bacitracin molecules in the compounds ofthe present invention.

FIGS. 5 and 5A illustrate the manner of bonding of each selenium ion toa corresponding bacitracin molecule in the compounds of the presentinvention. FIG. 5 illustrates generally the selenium bridge betweenadjacent cysteine and isoleucine amino acid residues of the bacitracinmolecule; FIG. 5A contains a more detailed illustration and shows themolecular structure of the cysteine and isoleucine amino acid residues.

DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT OF THE PRESENT INVENTION2. Compounds of Present Invention and Methods of Manufacture

Reference is now made to the drawings wherein like parts are representedwith like numerals throughout. The present invention relates tomultiprotein compounds and methods for treating psoriasis, arthritis,erythropoietic protoporphyria, and scar tissue and wounds. The variouschemical compounds used in these treatments are substantially similarand are generically represented by the multiprotein compound, generallydesignated 10, in FIG. 1.

As discussed in greater detail hereinafter, the multiprotein compoundsof the present invention include a variety of compounds having variouscombinations of beta-lactoglobulin proteins, alpha-lactalbumin proteins,and bacitracin proteins. However, for purposes of understanding thesemultiprotein compounds, the following discussion is in terms of apresently preferred species of these compounds.

With particular reference to FIG. 1, multiprotein compound 10 comprisesone molecule of beta-lactoglobulin 12, two molecules ofalpha-lactalbumin 14, and eight molecules of bacitracin 16. Thealpha-lactalbumin molecules 14 are linked to the beta-lactoglobulinmolecule 12 by a plurality of organic linkages 18. The bacitracinmolecules 16 are linked to the alpha-lactalbumin molecules 14 by aplurality of organic linkages 20. Multiprotein compound 10 preferablyfurther comprises eight selenium ions 24 (each having a +2 charge).Additionally, multiprotein compound 10 may optionally include, four zincions 22 (each having a +2 charge); when such zinc ions are present, eachzinc ion 22 is associated with two bacitracin molecules 16 so as to forma zinc salt therewith.

The various organic linkages between the proteins 12, 14, and 16 ofmultiprotein compound 10 are best illustrated in FIG. 2.Alpha-lactalbumin molecules 14 are linked to beta-lactoglobulin molecule12 by reacting the proteins with various alcohols to provide linkages31-34; examples of the alcohols are illustrated in FIGS. 3A-D. Thus,organic linkages 31-34 correspond to the organic linkages generallyrepresented as 18 in FIG. 1.

Still referring to FIG. 2, bacitracin molecules 16 are linked toalpha-lactalbumin molecules 14 by reacting the proteins with fatty acids(illustrated in FIG. 4) to form organic linkages 41-44. Thus, organiclinkages 41-44 of FIG. 2 correspond to the organic linkages generallyrepresented as 20 in FIG. 1.

Initially, it should be recognized that the representation of each ofproteins 12, 14, and 16 in FIG. 2 is general in nature, and there hasbeen no attempt to identify the individual amino acids in the longpolypeptide chains of proteins 12, 14, and 16. The R groups shown ineach of these polypeptide chains would, of course, correspond to those Rgroups actually present in the well-known sequence of amino acids foreach of these proteins. The wavy lines used in the illustration ofproteins 12, 14, and 16 in FIG. 2 simply represent continuations in thewell-known polypeptide chains. The straight lines at the end of each ofproteins 12, 14 and 16 in FIG. 2 simply represent the ends of eachpolypeptide chain. Finally, it should be noted that the two-dimensionalrepresentations of the proteins and organic linkages in both FIGS. 1 and2 are used for sake of clarity. In reality, these proteins and linkagesassume complex three-dimensional configurations, but no attempt has beenmade to illustrate any such three-dimensional configuration.

Referring now to FIGS. 2 and 3A-D, it will be seen that a variety ofalcohols may be used to form organic linkages 31-34 betweenbeta-lactoglobulin protein 12 and alpha-lactalbumin proteins 14. Suchalcohols include noncyclic aliphatic alcohols, steroid alcohols,triterpenoid alcohols, and thioglycerol. It will be recognized that thearrangement of organic linkages 31-34 of FIG. 2 is given by way ofillustration only, and is not intended to represent the order orfrequency of the different types of linkages as they may actually appearin multiprotein compound 10.

FIG. 3A shows a noncyclic aliphatic alcohol, generally designated 51,which reacts with proteins 12 and 14 to form organic linkage 31 of FIG.2. As seen in FIG. 3A, noncyclic aliphatic alcohol 51 has three radicalgroups (hereinafter referred to as "R" groups). R₁ and R₂ may behydrogen or any organic side chain which will not create sterichindrance problems and which is nontoxic when substituted inmultiprotein compound 10. It has been found that R₁ and R₂ shouldpreferably not be longer than about 50 carbon atoms in length, becausesteric hindrance becomes a substantial obstacle with such longer sidechains. R₃ can be any organic constituent having a chain of carbon atomsfrom about 6 to about 48 atoms in length such that the overall length ofnoncyclic aliphatic alcohol 51 is from about 8 to about 50 carbon atomsin length. Presently, the most preferred length for the carbon chain ofalcohol 51 and thus for organic linkage 31 is from about 14 to about 20carbon atoms long.

In the reaction of noncyclic aliphatic alcohol 51 with proteins 12 and14 to form organic linkage 31, the hydroxyl group of alcohol 51 reactswith an amino group on protein 12, thereby forming a water molecule in acondensation reaction so as to result in a carbon-to-nitrogen bond. Themethyl group of alcohol 51 holds a slightly positive electrical charge,and is thus electrostatically attracted and "bonded" to a correspondingnegatively charged carbonyl group on protein 14.

Conversely, it will be appreciated that the hydroxyl group of alcohol 51may react with an amino group of protein 14 and the methyl group ofalcohol 51 may associate with a carbonyl group of protein 12 to form asimilar linkage (not shown). The preference of one way or the other isinfluenced by such factors as steric hindrance and temperature. Theprobability of binding alcohols 51 (as well as alcohols 52-54) in agiven orientation depends in large part upon the velocity of the alcoholmolecules, which in turn depends on the thermal energy present(temperature) and on the size of the alcohol molecules (sterichindrance). Moreover, as the length of the alcohol molecule increases,the probability of that molecule forming a bond between proteins 14 and20 decreases since a longer molecule will have a slower velocity andthus less chance of forming a bond upon collision. Alcohols with carbonchains between about 14 and about 20 carbons have adequate length forbonding proteins 12 and 14, and steric hindrance at this length is not asignificant bond-prohibiting factor.

As seen in FIG. 3B, a steroid alcohol, generally designated 52, may beused to form organic linkage 32 of FIG. 2. Steroid alcohol 52 may be anyalcohol having the general configuration shown in FIG. 3B, includingthree possible R groups (R₄, R₅, and R₆) which comprise any number ofcarbon atoms such that the overall length of the longest carbon chain insteroid alcohol 52 is from about 8 to about 50 carbon atoms in length.Certain of the other R₄, R₅, or R₆ may not be required if the length ofthe other R groups is sufficient to provide the indicated length. Again,the preferred length for alcohol 52 is from about 14 to about 20 carbonatoms long because, as previously discussed herein, alcohols 52 whichare longer than 20 carbon atoms become increasingly difficult to bind toproteins 12 and 14 due to steric hindrance and the lower probability ofattaining the collision velocity needed for binding.

Steroid alcohol 52 reacts with proteins 12 and 14 much in the same wayas noncyclic aliphatic alcohol 51. As best illustrated in FIG. 2, thehydroxyl group of steroid alcohol 52 reacts with an amino group ofprotein 12, thereby forming a water molecule in a condensation reactionso as to result in a carbon-to-nitrogen bond. Similarly, each of the twoterminal methyl groups of steroid alcohol 52 associate with acorresponding carbonyl group of protein 14 by electrostatic attraction.As with alcohol 51, alcohol 52 may also serve to link proteins 12 and 14by reacting with an amino group of protein 14 and associating its methylgroups with the carbonyl groups of protein 12 to form a linkage (notshown) having an orientation inverse to that of linkage 32.

As seen in FIG. 3C, a triterpenoid alcohol, generally designated 53, maybe reacted with proteins 12 and 14 to form linkage 33 shown in FIG. 2.Triterpenoid alcohol 53 may be any alcohol having the generalconfiguration shown in FIG. 3C, including four R groups R₇, R₈, R₉, andR₁₀. The hydroxyl group of triterpenoid alcohol 53 reacts through acondensation reaction with an amino group of protein 12, as heretoforeexplained, to form a carbon-to-nitrogen bond. The methyl group attachedto R₁₀ of alcohol 53 associates with a carbonyl group of protein 14 inan electrostatic "bond" as heretofore explained. Moreover, the twomethyl groups attached to R₇ and R₈ may, but need not necessarily,associate electrostatically with carbonyl groups of protein 12.

R₉ and R₁₀ of triterpenoid alcohol 53 should be of such length toprovide an overall carbon chain of from about 8 to about 50 carbon atomslong, with the presently most preferred range being from about 14 toabout 20 carbon atoms long. Of course, this length could be providedentirely by either R₉ or R₁₀, thereby eliminating the necessity of theother R group. Alternatively, R₇ and R₈ may be of sufficient length(typically from about 1 to about 50 carbon atoms long) to allow forassociation of the methyl groups attached thereto with carbonyl groupsof protein 12, as shown in FIG. 2, or may be hydrogen and thus exhibitno such association. As with alcohols 51 and 52, triterpenoid alcohol 53may be reacted with proteins 12 and 14 in an orientation inverse to thatshown by linkage 33 in FIG. 2.

Due to the three-dimensional configuration of proteins 12 and 14, it ispossible, and often desirable, to provide relatively shorter organiclinkages between proteins 12 and 14 at those locations where theproteins are closest to each other. Such linkages can be provided byreacting thioglycerol molecules with proteins 12 and 14, one suchthioglycerol molecule 54 being illustrated in FIG. 3D. As best seen inFIG. 2, the two hydroxyl groups of thioglycerol molecule 54 react withamino groups on both proteins 12 and 14, in condensation reactions, toform linkage 34.

It will be appreciated that any combination of noncyclic aliphaticalcohols 51, steroid alcohols 52, and triterpenoid alcohols 53 may beused to form linkages 18 shown in FIG. 1. The illustration in FIG. 2 isgiven only to show the manner in which these alcohols bond to proteins12 and 14, not to suggest the sequence or relative quantities of eachtype of organic linkage formed thereby. Moreover, it should beunderstood that the organic linkages formed by reacting thioglycerolmolecules 54 with proteins 12 and 14 are not essential, but contributesignificantly to the overall stability of the multiprotein structure.

It will also be appreciated that the important chemical groups whichalcohols 51-54 need are the hydroxyl group and the methyl group whichreact to form linkages 31-34 as described herein. In fact, it has beenfound that fatty acids may also be used to form linkages 31-34. Sincethe carboxyl group of a fatty acid consists of a carbonyl group and ahydroxyl group, fatty acids also have the necessary chemical groups toform linkages 31-34.

It should be noted that where both alcohols and fatty acids areavailable to form organic linkages 31-34, the formation of linkages withthe alcohols is chemically preferred over linkages with the fatty acidssince the carbonyl portion of the fatty acid carboxyl groups tends todecrease the probability that a bond will be formed between proteins 12and 14.

As discussed hereinabove, each of organic linkages 31-34 in FIG. 2(linkages 18 in FIG. 1) are from about 8 to about 50 carbons in length,with the presently preferred range being from about 14 to about 20carbon atoms in length. It has been found that these linkages mustgenerally be at least about 8 carbon atoms long in order to be ofsufficient length to be structurally capable of linkingbeta-lactoglobulin proteins 12 and alpha-lactalbumin proteins 14.However, it should be recognized that the three-dimensionalconfiguration of certain compounds occasionally allows for shorterlinkages, such as the thioglycerol linkages 34.

The maximum length for each of linkages 31-34 is controlled in largepart by the desired stability of multiprotein compound 10. As the lengthof these linkages approaches 50 carbon atoms in length, it has beenfound that multiprotein compound 10 becomes increasingly less stable,thereby yielding a compound with a shortened lifetime. Compounds formedby using linkages in excess of about 50 carbon atoms in length arepossible, but are generally too unstable to be practical or viable. Thepresently preferred length of about 14 to about 20 carbon atoms forlinkages 31-34 yields multiprotein compounds 10 which are both stableand provide adequate support linkages between beta-lactoglobulinproteins 12 and alpha-lactalbumin proteins 14.

Referring now to FIGS. 2 and 4, organic linkages 41-44 are formed byreacting fatty acids, generally designated 60 in the generalrepresentation of FIG. 4, with alpha-lactalbumin molecules 14 andbacitracin molecules 16. The carboxyl group of each fatty acid 60 reactswith an amino group of either protein 14 or protein 16, thereby forminga water molecule and resulting in an amide bond. For example, thecarboxyl group of fatty acid 60 may react with an amino group of protein16 to form an amide bond therewith. The methyl group of fatty acid 60will then be electrostatically associate with a carbonyl group ofprotein 14 to form an organic linkage such as linkage 41 or 43.Conversely, the carboxyl group of fatty acid 60 can react with an aminogroup of protein 14, and its methyl group can become associated with acarbonyl group of protein 16, to form organic linkages such as linkages42 and 44.

As seen in FIG. 2, each of linkages 41-44 has an R group (designatedR₁₁, R₁₂, R₁₃, R₁₄, respectively). All of these R groups are representedgenerally by R in FIG. 4, and each of these R groups comprises a chainof carbon atoms from about 6 to about 48 carbon atoms long in order toprovide organic linkages 41-44 with carbon chains having a total lengthfrom about 8 to about 50 carbon atoms long. Presently, the mostpreferred length for each of the R groups is between 12 and 18 carbonatoms long, such that each of organic linkages 41-44 is from about 14 toabout 20 carbon atoms in length. Additionally, it will be appreciatedthat each of R₁₁, R₁₂, R₁₃, or R₁₄ may also have various carbon sidechains. R₁₁ -R₁₄ may be any component that may be desirable for aparticular application, e.g., vitamins, enzymes, or hormones.

It is also important to note that it is not essential that each of the Rgroups be of the same length; indeed, it has presently been found moredesirable to vary the lengths of each of these R groups so that linkages41-44 are of differing lengths. This arrangement provides better linkagebetween proteins 14 and 16 in their three-dimensional configurations andfurther acts as a cushion between the two proteins to provide a morestable and durable structure. Finally, it will be recognized that bothsaturated and unsaturated fatty acids may be used to form linkages41-44.

From the foregoing, it will be appreciated that the important chemicalgroups which each of fatty acids 60 need are the carboxyl and the methylgroup which react to form linkages 41-44 as described herein. It will befurther appreciated that alcohols such as alcohols 51-54 may be used toform linkages between alpha-lactalbumin proteins 14 and bacitracinproteins 16, in lieu of or in combination with the fatty acids discussedhereinabove. Such alcohols would form linkages in a similar fashion tolinkages 31-34, discussed herein. For reasons similar to those discussedabove with respect to organic linkages 31-34, the preferred length fororganic linkages 41-44 is from about 14 to about 20 carbon atoms inlength.

FIGS. 5 and 5A illustrate the bonding of each of the selenium ions inthe compounds of the present invention to a corresponding bacitracinmolecule. More particularly, FIGS. 5 and 5A provide an illustration ofthe bonding of a selenium ion 24 to the terminal cysteine and isoleucineamino acid residues which are found on each bacitracin molecule 16. Theisoleucine residue is at the amino terminal end of bacitracin molecule16 (at the right of FIGS. 5 and 5A) and the cysteine residue is the nextamino acid residue in the bacitracin chain of amino acids (shown at theleft of FIGS. 5 and 5A). Thus, FIGS. 5 and 5A represent only a smallportion (the terminal two amino acids) of the long polypeptide chainwhich makes up each bacitracin molecule 16 illustrated in FIG. 1. (Thewavy line in FIG. 5A is a representation of the continuation of thepolypeptide chain).

In a typical bacitracin molecule, the sulfhydryl group of the cysteineresidue and the carbonyl group of the isoleucine residue exhibit a typeof tautomerism in which the hydrogen of the sulfhydryl group istransferred to the carbonyl group to form a hydroxyl group while forminga sulfide bridge between the cysteine and the isoleucine residues. Inthe present invention, each selenium ion is substituted for the sulfuratom which is normally associated with the sulfide bond between theadjacent isoleucine and cystine amino acid residues of each bacitracinmolecule. This substitution results in a selenium bridge between thecysteine and isoleucine residues, thereby forming a molecule ofseleno-bacitracin.

Referring now again to FIG. 1, zinc ions 22 may be included inmultiprotein compound 10 in order to link adjacent bacitracin molecules16 in an ionic bond. Each zinc ion 22 associates with a negativelycharged carboxyl group on each of two adjacent bacitracin molecules 16to form the zinc salt. Zinc ions 22 add desirable chemical stability tothe overall structure of multiprotein compound 10. Therefore, thepresence of zinc ions 22 results in a slow down of the normaldegradation processes and an increase in the effective lifetime of themultiprotein compounds.

It should be noted that the exact location of each of organic linkages18 and 20 of FIG. 1 (corresponding to organic linkages 31-34 and 41-44of FIG. 2, respectively) is determined in large part by the reactionconditions under which multiprotein compound 10 is formed; the presentlypreferred reactions are explained hereinafter. By carefully controllingthe reaction conditions, the actual amino acid residues which providethe sites for such linkages may be predicted with surprising accuracy.

Although the preferred procedure for preparing the compounds of thepresent invention may differ slightly according to the end use for whichthe compound is intended, the following components listed in Table Ibelow and the methods of manufacture discussed hereinafter are given byway of general instruction to enable those of ordinary skill in the artto make multiprotein compounds which are within the scope of the presentinvention.

                  TABLE I                                                         ______________________________________                                                             Weight % of Compound                                     Component            (preferred range)                                        ______________________________________                                        beta-lactoglobulin   40-60%                                                   alpha-lactalbumin    10-20%                                                   fatty acids           5-31%                                                   zinc bacitracin      11-25%                                                   selenium (either as Se° or SeS)                                                             0.5-1%                                                   lanolin U.S.P. (hydrous or anhydrous)                                                               7-20%                                                   ______________________________________                                    

As listed above, the important components of the multiprotein compoundsof the present invention include beta-lactoglobulin, alpha-lactalbumin,fatty acids, zinc bacitracin, selenium (either as selenium alone or asselenium monosulfide), and lanolin U.S.P. (either hydrous oranhydrous--there is presently no known reason for preferring one overthe other). Lanolin U.S.P. is an important component only in that itprovides a source for the noncyclic aliphatic 51, steroid 52, andtriterpenoid 53 alcohols used to form linkages 18 and for some of thefatty acids which form linkages 20. However, it should be noted thatother sources for alcohols 51-53 and fatty acids 60 may be employed inlieu of lanolin U.S.P. Moreover, it should be further noted that estersof alcohols 51-53 and fatty acids 60 may be employed in lieu of or incombination with alcohols 52-53 and fatty acids 60 in makingmultiprotein compounds within the scope of the present invention, theester bonds of such compounds being hydrolyzed during the manufacturingprocedure to yield the alcohols and fatty acids used to form linkages31-34 and 41-44, respectively.

Other components are often desirable in the manufacture of the compoundsof the present invention, but are not critical to the function of thecompounds of the present invention for their intended purpose. Forexample, tartaric and benzoic acid may be added to function aspreservatives; these organic acids act to kill the lactobacillusbacteria which feed on the beta-lactoglobulin and the alpha-lactalbuminproteins. petrolatum U.S.P. may be added to the compounds of the presentinvention as an emollient or protectorate for the skin and to providestabilization for the organic linkages 20 between proteins 14 and 16 ofthe present invention. ("Medium" petrolatum U.S.P. is presentlypreferred over "heavy" or "light" petrolatum U.S.P. since mediumpetrolatum U.S.P. contains a greater variety of different lengths oforganic components which tends to augment the stabilization of linkages20.) Ethanol may also be added to break the micelles in the petrolatumand lanolin (either anhydrous or hydrous), thereby reducing thetemperature required for making the compounds of the present invention.

Glycerol may be added as a component in order to provide thioglycerolwhen it is desirable to form organic linkages between proteins 12 and 14such as linkage 34. To generate the thioglycerol needed to form theselinkages, glycerol and selenium monosulfide (instead of selenium alone)are preferably used to make the multiprotein compound 10, because thesulfur from the selenium monosulfide is released and subsequentlycombined with the glycerol to form thioglycerol.

One procedure for combining the above-identified components tomanufacture the multiprotein compounds of the present invention is asfollows: A first fraction is prepared by heating the lanolin U.S.P. toabout 30°-55° C., with the presently preferred range being about 35°-40°C. If petrolatum U.S.P. is to be included, the petrolatum is mixed withthe lanolin before heating to this temperature. Additionally, theoptional ethanol and glycerol ingredients, if used, are added to thepetrolatum-lanolin mixture, while maintaining the temperature betweenabout 30°-55° C. (preferably at about 35°-40° C.) Although it ispossible to prepare the first fraction at temperatures above about 55°C., substantial oxidation of the alcohol and fatty acid components oflanolin tends to make such elevated temperatures undesirable.Temperatures of at least about 30° C. are typically needed, however, toprovide the necessary thermal energy to break up the lanolin micelles.

In a separate receptacle, a second fraction is prepared by first mixingthe fatty acids together with a basic buffer solution. By thisprocedure, the fatty acids are converted into potassium or sodium saltsin a neutralization reaction. This neutralization reaction is typicallyconducted at a temperature within the range of about 20°-25° C. for aperiod of about 2-3 hours. The buffer solution may comprise, forexample, such basic constituents as sodium carbonate, sodiumbicarbonate, potassium carbonate, potassium bicarbonate, or combinationsthereof. Enough of a basic buffer is added to the acidic mixture tobring the pH of the mixture within the range of about 4.0-5.8, thepresently preferred pH being about 5.5. Next, the optional preservativeingredients, benzoic acid and tartaric acid, are blended with the fattyacid salts and the pH is again adjusted to about 4.0-5.8 by adding morebuffer. Thereafter, the components of both the first and secondfractions are mixed together and allowed to react for a period of atleast about 2 hours, while maintaining the pH at about 4.0-5.8 andcooling the mixture to about 20°-40° C., preferably within the range ofabout 25°-30° C.

Although it is possible to conduct the above procedure at pH valuesgreater than about 5.8, the formation of organic linkages 31-34 and41-44 decreases substantially at pH values higher than about 5.8. Also,it has been found that the final pH value for the multiprotein compoundshould not be lower than about 4 or higher than about 8 sincemultiprotein compounds having these pH values tend to cause undesirableacid-base reactions with the skin and body cells and also have shortershelf-lives.

Moreover, it should be recognized that although the above-describedprocedure contains several buffer addition steps to maintain the pHwithin the preferred range of about 4.0-5.8 while forming the organiclinkages, the procedure may be conducted using only one such bufferaddition step or as many as desired in order to adjust the pH to about4.0-5.8. It is preferable, however, to monitor and adjust the pH inseveral steps to ensure that the pH is indeed within the preferred rangeso as to ensure proper formation of the organic linkages. Finally, it isimportant to note that once the organic linkages are formed, thepreferred range for the final pH of the multiprotein compound made isabout 4.0-8.0.

While maintaining the mixture at a temperature within the range of about20°-40° C. (preferably within the range of about 25°-30° C.), the zincbacitracin and selenium monosulfide (or selenium alone) are introducedinto the mixture and blended therewith. The resulting mixture is thencooled to room temperature, and the beta-lactoglobulin andalpha-lactalbumin are thoroughly blended into the mixture. Again, the pHshould be monitored and adjusted, if necessary, with the buffer solutionso as to maintain the pH at about 4.0-5.8 and enable the organiclinkages to form.

In one preferred embodiment, the final pH of multiprotein compound 10 isabout 5.5. By making multiprotein compound 10 with a final pH of about5.5, the compound will be absorbed more readily by the skin whichnormally also has a pH of about 5.5. It will be recognized, however,that multiprotein compound 10 can be made in active form at different pHvalues, and that the adjustment of the pH to about 5.5 is used merely torender the compound more suitable for topical application. Moreover, apH of about 5.5 is extremely suitable for surgical application orinjection since such a pH enhances absorption of multiprotein compound10 into the cells themselves. Cell membranes and cell nuclei generallyhave a pH of about 5.5, while the cytoplasm of most cells has a pHsomewhere around 7.2. When multiprotein compound 10 is made with a pH ofabout 5.5, the natural pH differential in the cells creates an osmoticdriving force which enhances absorption of the multiprotein compound bythe cells.

In some instances, it may be desirable to make zinc seleno-bacitracinalone, without lactoglobulin proteins 12, lactalbumin proteins 14, andlinkages 18 and 20. To make such zinc seleno-bacitracin compounds, zincbacitracin and selenium (either in the form of selenium monosulfide orselenium alone) are mixed together in a suitable medium while preferablymaintaining the pH within the range of about 4.0-5.8 (the presentlypreferred pH being about 5.5) at a temperature within the range of about20°-50° C. (the presently preferred range being about 25°-30° C.). Onesuitable medium for making zinc seleno-bacitracin is the mixture offractions one and two described above with respect to the manufacture ofthe multiprotein compound 10.

It should be recognized, however, that other mediums are also suitablefor making zinc seleno-bacitracin. A suitable medium is generally anymedium which is both amphocellic and hydrophilic. The amphocellic natureof the medium refers to the fact that the medium is both water and oilsoluble. The primary reason that an amphocellic medium is presentlypreferred is that bacitracin is amphocellic; thus, an amphocellic mediumis needed to effectively solvate the zinc bacitracin used to manufacturezinc seleno-bacitracin. Moreover, when selenium monosulfide (instead ofselenium alone) is reacted with the zinc bacitracin to form zincseleno-bacitracin, removal of water from the reaction medium tends topromote the reaction. Thus, a hydrophilic reaction medium is preferredwhen selenium monosulfide is used as the selenium reactant.

The chemical equations for reacting zinc bacitracin with seleniummonosulfide (reaction A), or alternatively, with selenium alone(reaction B), are as follows: ##STR1## By adding glycerol to thereactants side of equation A or B, thioglycerol is also produced,together with the zinc seleno-bacitracin, since the glycerol traps thesulfide ions released from the zinc bacitracin (reactions A and B) andfrom the selenium monosulfide (reaction A). Generally, it is preferredto use selenium monosulfide when thioglycerol is a desired product sincethe use of selenium monosulfide provides twice as much available sulfurfor the production of thioglycerol than where selenium alone is used.

Whenever the term "zinc seleno-bacitracin" is used herein, it will berecognized that this refers to the zinc salt of seleno-bacitracin. Also,it will be recognized that, depending upon the compound to be produced,seleno-bacitracin may be substituted for zinc seleno-bacitracin. Asdiscussed above, the zinc functions mainly to stabilize the structure ofmultiprotein compound 10 and to allow the compound 10 to be subjected tohigher temperatures without undergoing degradation. Accordingly, thereactions for forming seleno-bacitracin are similar to those for zincseleno-bacitracin:

    SeS+bacitracin→seleno-bacitracin+2S.sub.2.sup.2-    (C)

    Se+bacitracin→seleno-bacitracin+S.sub.2.sup.2-      (D)

Moreover, it should be recognized that other cations may be used in lieuof zinc ions to form a salt with the bacitracin molecules and therebyprovide additional stability to multiprotein compound 10. For example,any cations having a 2+ charge which are nontoxic to the body may beused, e.g., Ca²⁺, Ba²⁺, Fe²⁺, Mn²⁺, Mg²⁺, etc.

The relative proportions of the components used to make the multiproteincompounds of the present invention may vary somewhat from theproportions given above, according to the intended use of the compound.Examples of compounds which are within the scope of the presentinvention are given hereinbelow.

EXAMPLE 1

A multiprotein compound within the scope of the present invention wasmade by combining the following components in the indicated amounts:

    ______________________________________                                        Component           Amount (grams)                                            ______________________________________                                        beta-lactoglobulin  40       g.                                               alpha-lactalbumin   10       g.                                               fatty acids         14.5     g.                                               zinc bacitracin     11.5     g.                                               selenium monosulfide                                                                              1.0      g.                                               lanolin U.S.P.      11.5     g.                                               tartaric acid       1        g.                                               benzoic acid        2        g.                                               petrolatum U.S.P.   6        g.                                               ethanol (70%)       0.5      g.                                               glycerol            2.5      g.                                               ______________________________________                                    

These components were combined according to the following procedure: Afirst fraction was prepared by mixing the lanolin U.S.P., petrolatumU.S.P., ethanol, and glycerol together and the mixture was heated to andmaintained at a temperature of about 40° C.

In a separate receptacle, a second fraction was prepared by first mixingthe fatty acids (in the present example, 10 grams of stearic acid and4.5 grams of oleic acid), tartaric acid, and benzoic acid together withabout 2.1 grams of a buffer solution comprising 40% sodium carbonate ata temperature of about 25° C., the resulting pH of the mixture beingabout 5.5. This component mixture comprising the second fraction wascontinuously blended for a period of about 2.5 hours while maintainingthe temperature at about 25° C. Thereafter, the components of the firstand second fractions were mixed together and allowed to react, while thepH was maintained at about 5.5 by adding more of the buffer solution (inthis example, about 0.1 grams) and the resulting mixture was allowed tocool to about 30° C.

While maintaining the mixture at 30° C., the zinc bacitracin andselenium monosulfide were introduced into the mixture and blendedtherewith. The resulting mixture was then cooled to room temperature,i.e. about 22° C., and the beta-lactoglobulin and alpha-lactalbumin werethoroughly blended into the mixture. The pH was again adjusted to about5.5 by adding more of the sodium carbonate buffer solution (in thisexample, about 0.15 grams). This reaction mixture was allowed to reactfor a period of about 2.5 hours, thereby forming a multiprotein compoundwithin the scope of the present invention.

EXAMPLE 2

A zinc seleno-bacitracin compound within the scope of the presentinvention was made by combining the following components in theindicated amounts:

    ______________________________________                                        Component           Amount (grams)                                            ______________________________________                                        zinc bacitracin     28.85    g.                                               selenium monosulfide                                                                              2.22     g.                                               lanolin U.S.P.      100      g.                                               ______________________________________                                    

These components were combined according to the following procedure: Thezinc bacitracin was mixed together with the selenium monosulfide in thelanolin U.S.P. medium (lanolin provides a suitable amphocellic andhydrophilic medium for carrying out the procedure), and the mixture washeated to about 35° C. This mixture was allowed to react for a period ofabout 2.5 hours, thereby producing a zinc seleno-bacitracin compoundwithin the scope of the present invention. The pH of the compound wasthen adjusted to about 5.5 by the addition of 2.5 grams of solid sodiumbicarbonate.

EXAMPLE 3

A zinc seleno-bacitracin compound within the scope of the presentinvention was made by combining the following components in theindicated amounts:

    ______________________________________                                        Component          Amount (grams)                                             ______________________________________                                        zinc bacitracin    28.85    g.                                                selenium           1.57     g.                                                lanolin U.S.P.     150      g.                                                oleic acid         50       g.                                                ethylene glycol    5        g.                                                ______________________________________                                    

These components were combined according to the following procedure: Thezinc seleno-bacitracin and selenium were mixed together with the lanolinand oleic acid, the lanolin and oleic acid serving as the reactionmedium. The ethylene glycol was added to the mixture and the mixture washeated to about 40° C. and allowed to react for a period of about 2.5hours, thereby producing a zinc seleno-bacitracin compound (with a pH ofabout 5.6) within the scope of the present invention. In this example,the ethylene glycol serves to trap the sulfur ions released from thezinc bacitracin, thereby eliminating unpleasant sulfur odors.

EXAMPLE 4

A seleno-bacitracin compound within the scope of the present inventionwas made by combining the following components in the indicated amounts:

    ______________________________________                                        Component           Amount (grams)                                            ______________________________________                                        bacitracin          28.2     g.                                               selenium monosulfide                                                                              2.22     g.                                               petrolatum U.S.P.   100      g.                                               stearic acid        15       g.                                               cholesterol         35       g.                                               glycerol            10       g.                                               ______________________________________                                    

These components were combined according to the following procedure: Thebacitracin and selenium monosulfide were mixed together with thepetrolatum, stearic acid, and cholesterol, the petrolatum, stearic acid,and cholesterol serving as the reaction medium. The glycerol was addedto the mixture and the mixture was heated to about 30° C. and allowed toreact for about 2.5 hours, thereby producing a seleno-bacitracincompound (with a pH of about 5.8) within the scope of the presentinvention. The glycerol in the foregoing example serves merely to trapthe sulfur ions released from the bacitracin and selenium monosulfide,thereby eliminating unpleasant sulfur odors.

The multiprotein compounds of the present invention have exhibitedantimitotic activity in slowing down the proliferation of corneocyteswithout harming normal cells. The active ingredient of multiprotein 10in treating psoriasis is believed to be the zinc seleno-bacitracin. Inparticular, the zinc seleno-bacitracin molecules to act to deliverselenium ions to the deoxyribonucleic acid of the corneocytes so as toprohibit mitosis.

During the early stages of mitosis, it is believed that negative chargeson each of the deoxyribonucleic acid strands cause the deoxyribonucleicacid to begin to unwind, thus beginning replication. By delivering aselenium ion (having a +2 charge) to the deoxyribonucleic acid, theselenium ion becomes incorporated into one of the deoxyribonucleic acidstrands, thereby imparting a net positive charge to that strand andcausing the two strands to be attracted together, instead of beingrepelled as is needed for the unwinding action of replication. In thismanner, the selenium ion can prohibit the replication of thedeoxyribonucleic acid, and thus the replication of the corneocytes. Aswill be discussed hereinafter, this action of the selenium ions does notaffect the normal growth of normal cells.

The bacitracin molecule 16 provides a chemical transport structure foreach selenium ion 24; each bacitracin molecule delivers the selenium ionto the deoxyribonucleic acid of a corneocyte. The alpha-lactalbuminprotein 14 and beta-lactoglobulin protein 12 with their accompanyinglinkages 20 and 18, provide a chemical support structure for the zincseleno-bacitracin.

Moreover, the alpha-lactalbumin protein 14 provides a means foreffectuating entry of multiprotein compound 10 into the corneocytes.This is made possible by the hydrolyzing properties of alpha-lactalbuminprotein 14. Alpha-lactalbumin protein 14 acts to hydrolyze the beta-1→4linkages between N-acetylmuramic acid and2-acetylamino-2-deoxy-D-glucose in mucopolysaccharides and mucopeptidesand to break the bonds in teichoic acid. These constituents are allimportant components in the structure of the cell wall, and uponhydrolyzation thereof, allow entry of the multiprotein compound into thecell.

After hydrolyzing the cell wall structure to allow entry of themultiprotein compound into the cell, the hydrolysis performed by thealpha-lactalbumin protein 14 is reversed to restore the cell wall. Thereverse hydrolysis or restoration of the cell wall is accomplished bythe bacitracin portion of the zinc seleno-bacitracin. Bacitracin has thecapacity to absorb a significant amount of water and thus acts to absorbthe water molecules which were added to the cell wall during hydrolysis,thereby reversing the hydrolysis and restoring the cell wall to itsoriginal stature. Thus, the multiprotein compound of the presentinvention provides means for entering the cell without harming thecellular structure.

The beta-lactoglobulin protein 12 of the multiprotein compound addsstability to the overall structure of the compound. More importantly, incombination with organic linkages 18, beta-lactoglobulin protein 12 actsto increase the hydrolyzing activity of alpha-lactalbumin protein 14 byslowing down the rotational movement about the carbon-to-carbon bonds ofthe polypeptide chain of alpha-lactalbumin protein 14 by a factor of atleast 100. Thus, beta-lactoglobulin protein 12 and linkages 18 serve toenhance the capacity of alpha-lactalbumin protein 14 to hydrolyze thecell wall and facilitate entry of multiprotein compound 10 into thecell.

Once inside the cell, it is believed that cellular enzymes act tohydrolyze the bonds between linkages 18 and beta-lactoglobulin protein12 so as to detach beta-lactoglobulin protein 12 from the remainder ofthe structure of multiprotein compound 10. Beta-lactoglobulin proteins12 are subsequently attacked by cellular proteinases which degrade theseproteins 12 into amino acids which can be used by the body. Further, thepositively charged selenium ion and the positively charged methyl groupson the free ends of linkages 18 (once detached from beta-lactoglobulinprotein 12) can be attracted to the negatively charged deoxyribonucleicacid in the nucleus of the cell, thereby providing the necessary drivingforce for delivering the selenium ion to the deoxyribonucleic acid.

Upon arrival of the deoxyribonucleic acid, the remaining portion ofmultiprotein compound 10 releases the selenium ion which combines withthe deoxyribonucleic acid to stop replication thereof. The remainingportion of multiprotein compound 10 is then attacked by proteinases andother enzymes found in the cell to yield amino acids (originating fromproteins 14 and 16), fatty acids (originating from linkages 20), and avariety of alcohols (originating from linkages 18) which maysubsequently be used by the body. Thus, the multiprotein compound of thepresent invention is broken down like any other protein to be used asfood and to provide amino acids for the manufacture of other proteinsneeded by the body.

Importantly, since the multiprotein compound enters normal cells as wellas corneocytes, it should be noted that the multiprotein compound doesnot act to destroy any cells, whether corneocytes or normal cells, butrather acts to prohibit proliferation and growth of the corneocytesalone. This is believed to be due to the fact that the selenium ions 24delivered by the multiprotein compound only act momentarily to prohibitreplication of the deoxyribonucleic acid, thereby giving the corneocytesenough time to repair and rehabilitate themselves into normal cells.

The abnormal or rapid proliferation of corneocytes which causespsoriasis results in corneocytes which are often deficient. Deficientcorneocytes generally have the capacity to be repaired or rehabilitated,but usually cannot repair themselves without some assistance. Since, aswill be discussed in greater detail hereinafter with regard to scartissue and wound healing, the multiprotein compounds of the presentinvention provide most, if not all, of the raw materials necessary tohelp the deficient corneocytes repair themselves, multiprotein compound10 actually promotes the repair of the deficient corneocytes into"normal" cells. Thus, the multiprotein compounds give the deficientcorneocytes time to repair themselves before further replication ofthese cells can occur and further act to actually promote such repair,while leaving the normal cells unharmed.

The following components listed in Table II below and examples discussedhereinafter are given by way of general instruction to enable those ofordinary skill in the art to make other multiprotein compounds withinthe scope of the present invention.

                  TABLE II                                                        ______________________________________                                                           Weight % of Compound                                       Component          (preferred range)                                          ______________________________________                                        beta-lactoglobulin 40-60%                                                     alpha-lactalbumin  10-20%                                                     fatty acids         5-20%                                                     zinc bacitracin    15-24%                                                     selenium (either as Se° or SeS)                                                           0.7-1.0%                                                   glycerol           1-5%                                                       tartaric acid      1-3%                                                       lanolin U.S.P.      7-15%                                                     ______________________________________                                    

The components listed above are combined in the same manner as outlinedin Example I, with the exception that certain of the components ofExample I are omitted. It should be noted that although preferred rangesare given for glycerol and tartaric acid, these components are purelyoptional when making a multiprotein compound within the scope of thepresent invention.

EXAMPLE 5

A multiprotein compound within the scope of the present invention wasmade according to the procedure of Example 1, except that the componentswere combined in the following amounts:

    ______________________________________                                        Component            Amount (grams)                                           ______________________________________                                        beta-lactoglobulin   48       g.                                              alpha-lactalbumin    12       g.                                              fatty acids          6        g.                                              zinc bacitracin      24       g.                                              selenium monosulfide 1.4      g.                                              glycerol             1        g.                                              tartaric acid        1        g.                                              lanolin U.S.P. (anhydrous)                                                                         7        g.                                              ______________________________________                                    

In this example, the fatty acids used were oleic acid (5 grams) andpalmitic acid (1 gram).

EXAMPLE 6

Another multiprotein compound within the scope of the present inventionwas made according to the procedure of Example 5, except that 0.5 gramsof ethanol were added to the lanolin. The addition of ethanol aids inbreaking up the lanolin micelles.

2. Methods of Treatment

A. Psoriasis

The action of the multiprotein compounds of the present invention in thetreatment of psoriasis is believed to be as follows. It is believed thatmultiprotein compound 10 acts to prohibit replication of thedeoxyribonucleic acid in the corneocytes (white skin cells), therebyslowing down proliferation of the corneocytes while leaving normal cellsunharmed. Multiprotein compound 10 accomplishes this by providing amechanism for transporting selenium ions to the deoxyribonucleic acid inthe corneocytes so as to prevent unwinding and thus replication of thedeoxyribonucleic acid.

The following components listed in Table III below and example discussedhereinafter are given by way of general instruction to enable those ofordinary skill in the art to make multiprotein compounds within thescope of the present invention which may be used in the treatment ofpsoriasis.

                  TABLE III                                                       ______________________________________                                                           Weight % of Compound                                       Component          (preferred range)                                          ______________________________________                                        beta-lactoglobulin 40-60%                                                     alpha-lactalbumin  10-20%                                                     fatty acids         5-20%                                                     zinc bacitracin    12-20%                                                     selenium (either as Se° or SeS)                                                           0.5-0.7%                                                   lanolin U.S.P.      7-20%                                                     petrolatum U.S.P.  0-5%                                                       glycerol           0-4%                                                       tartaric acid      1-3%                                                       benzoic acid       1-5%                                                       ethanol            0.5-1%                                                     ______________________________________                                    

The components listed above are combined in the same manner as outlinedin Example 1. It should be noted that although preferred ranges aregiven for petrolatum, glycerol, tartaric acid, benzoic acid, andethanol, these components are purely optional when making a multiproteincompound within the scope of the present invention for the treatment ofpsoriasis.

EXAMPLE 7

A multiprotein compound within the scope of the present invention whichhas been used in the treatment of psoriasis was made according to theprocedure of Example 1, except that the components were combined in thefollowing amounts:

    ______________________________________                                        Component           Amount (grams)                                            ______________________________________                                        beta-lactoglobulin  48       g.                                               alpha-lactalbumin   12       g.                                               fatty acids         7        g.                                               zinc bacitracin     19.3     g.                                               selenium monosulfide                                                                              0.8      g.                                               lanolin U.S.P. (hydrous)                                                                          7        g.                                               petrolatum U.S.P.   2.5      g.                                               glycerol            1        g.                                               tartaric acid       1        g.                                               benzoic acid        1.5      g.                                               ethanol             0.5      g.                                               ______________________________________                                    

In this example, the fatty acids used were stearic acid (5 grams) andoleic acid (2 grams). This multiprotein compound has been used for thetreatment of psoriasis. The daily dosage for such applications rangesfrom about 0.001-0.2 g/cm² of skin treated. A typical treatment usingthis multiprotein compound would include two daily topical applicationsof 0.04-0.1 grams of the compound per square centimeter of skin treated.

Although animal studies are continuing, at least a dozen psoriasispatients have received treatment using the compound of Example 7. Markedimprovements in the conditions of these patients were noted within threeweeks of treatment.

B. Arthritis

When used in the treatment of arthritis, the active ingredient of themultiprotein compounds of the present invention is believed to be thealpha-lactalbumin protein 14. Alpha-lactalbumin protein 14 acts to breakup polymerized collagen which is the major cause of arthritis.Alpha-lactalbumin protein portion 14 of multiprotein compound 10accomplishes this by hydrolyzing the glucosyl linkages in thepolymerized collagen, and also acts to prohibit further polymerizationof the collagen.

The beta-lactoglobulin protein 12, and further the bacitracin proteins16, act primarily to stabilize the overall structure of multiproteincompound 10 and increase the hydrolyzing activity of alpha-lactalbuminprotein 14 when used in the arthritis treatment of the presentinvention. Under normal conditions, it has been found thatalpha-lactalbumin by itself will only hydrolyze about 3% of polymerizedcollagen, the hydrolyzing activity of alpha-lactalbumin alone beingrelatively limited. However, when alpha-lactalbumin is linked tobeta-lactoglobulin by a plurality of organic linkages within the scopeof the present invention, a much higher percentage of hydrolysis, if notnearly complete hydrolysis, of the polymerized collagen is achieved.

The following components listed in Table IV below and examples discussedhereinafter are given by way of general instruction to enable those ofordinary skill in the art to make multiprotein compounds within thescope of the present invention which may be used in the treatment ofarthritis.

                  TABLE IV                                                        ______________________________________                                                           Weight % of Compound                                       Component          (preferred range)                                          ______________________________________                                        beta-lactoglobulin 40-60%                                                     alpha-lactalbumin  10-20%                                                     fatty acids         5-31%                                                     zinc bacitracin    12-24%                                                     selenium (either as Se° or SeS)                                                           0.5-1.0%                                                   lanolin U.S.P.      7-20%                                                     glycerol           1-5%                                                       tartaric acid      0-3%                                                       benzoic acid       1-5%                                                       ethanol            0.5-1.5%                                                   ______________________________________                                    

The components listed above are combined in the same manner as outlinedin Example 1, with the exception that certain of the components ofExample 1 are omitted. It should be noted that although preferred rangesare given for zinc bacitracin, selenium, glycerol, tartaric acid,benzoic acid, and ethanol, these components are purely optional whenmaking a multiprotein compound within the scope of the present inventionfor the treatment of arthritis.

EXAMPLE 8

A multiprotein compound within the scope of the present invention whichhas been used in the treatment of arthritis was made according to theprocedure of Example 1, except that the components were combined in thefollowing amounts:

    ______________________________________                                        Component            Amount (grams)                                           ______________________________________                                        beta-lactoglobulin   53.5     g.                                              alpha-lactalbumin    13.5     g.                                              fatty acids          10       g.                                              zinc bacitracin      11       g.                                              selenium monosulfide 1.4      g.                                              lanolin U.S.P. (anhydrous)                                                                         7        g.                                              glycerol             1        g.                                              tartaric acid        1        g.                                              benzoic acid         2        g.                                              ethanol              0.5      g.                                              ______________________________________                                    

In this example, the fatty acids used were stearic acid (8 grams) andoleic acid (2 grams). It should be noted that the addition of petrolatumU.S.P. is not generally desirable when preparing multiprotein compoundsfor the treatment of arthritis. This is because substantial quantitiesof petrolatum tend to decrease the hydrolyzing activity ofalpha-lactalbumin and such hydrolyzing activity is a key factor in thetreatment of arthritis.

It should also be recognized that the zinc seleno-bacitracin portion ofmultiprotein compound 10 is optional when using the multiproteincompound for the treatment of arthritis. The bacitracin proteins 16 andlinkages 20 do act to further enhance the hydrolyzing properties ofalpha-lactalbumin proteins 14, but the multiprotein compound has beenfound to be effective in treating arthritis without the bacitracinproteins 16, organic linkages 20, and selenium ions 24. (The seleniumions 24 do not act to increase hydrolyzing activity, but may bedesirable for other reasons, e.g., some of the selenium ions may beconverted into trimethyl selenonium which is beneficial to the body.)

EXAMPLE 9

A multiprotein compound within the scope of the present invention usefulin the treatment of arthritis was made by combining the followingcomponents in the following amounts:

    ______________________________________                                        Components          Amount (grams)                                            ______________________________________                                        beta-lactoglobulin  60       g.                                               alpha-lactalbumin   16.5     g.                                               fatty acids         8.5      g.                                               lanolin U.S.P.      8.5      g.                                               tartaric acid       1.0      g.                                               ethanol (95%)       0.5      g.                                               safflower oil       5.0      g.                                               ______________________________________                                    

In this example, the fatty acids used were stearic acid (3.5 grams),arachidonic acid (1 gram), and linoleic acid (4 grams). These componentswere combined according to the following procedure: A first fraction wasprepared by mixing the lanolin U.S.P., safflower oil, and ethanoltogether, and the mixture was heated to and maintained within atemperature range of about 35°-40° C.

In a separate receptacle, a second fraction was prepared by mixing thefatty acids and tartaric acid together with about 1.6 grams of solidpotassium carbonate buffer at a temperature of about 23° C., theresulting pH of the mixture being about 5.5. This component mixturecomprising the second fraction was continuously blended for a period ofabout 2.5 hours while maintaining the temperature at about 23° C.Thereafter, the components of the first and second fractions were mixedtogether and allowed to react, while the pH was maintained at about 5.5by adding about 0.2 grams of a solid sodium carbonate buffer and theresulting mixture was allowed to cool to about 23° C.

In another receptacle, a third fraction was prepared by mixing thebeta-lactoglobulin and alpha-lactalbumin together at a temperature ofabout 23° C. The third fraction was then added to the already combinedfirst and second fractions and blended thoroughly. The pH was againadjusted by adding 0.1 grams of solid potassium carbonate buffer. Thismixture was allowed to react for a period of about 2.5 hours, therebyproducing a multiprotein compound within the scope of the presentinvention which is useful in the treatment of arthritis.

Although application by injection is also possible, the multiproteincompound 10 is generally applied topically when used to treat arthritis.When applied topically, multiprotein compound 10 penetrates the skin andreaches the arthritic joint within about ten (10) to about fifteen (15)minutes. Thus, although injection of the multiprotein compound 10directly into the joints is equally effective, topical application isoften preferred because of the relative convenience of application.Topical applications should provide a daily dosage of about 0.001-0.2grams per square centimeter (g/cm²) of skin. A presently preferredmethod for applying the multiprotein compound 10 to arthritis comprisesapplying 0.04-0.1 g/cm² of the compound to the skin twice daily. Suchtreatment should continue on a daily basis until the arthritic paindisappears and freedom of movement is restored.

While additional studies are in progress, at least two individuals havebeen treated for arthritis using the compound of Example 8. Both ofthese individuals had severe diagnosed cases of arthritis, the symptomsof which cleared up after regular treatment over a period of about threeweeks with this multiprotein compound.

C. Erythropietic Protoporphyria

The multiprotein compounds of the present invention have been found tobe effective in treating the symptoms of erythropoietic protoporphyria.As porphyrin IX accumulates in the cells (as is characteristic oferythropoietic protoporphyria), the porphyrin IX reacts with the cellwalls, causing a swelling and splitting of the skin. The multiproteincompounds of the present invention act to alleviate such swelling andsplitting. Although the exact mechanism for this action is notcompletely understood, it is believed that in the treatment oferythropoietic protoporphyria, the active ingredients of themultiprotein compounds are beta-lactoglobulin protein 12 and linkages 18attached thereto. As the multiprotein compound enters the cell, thepresence of porphyrin IX is believed to cause the bonds between linkages18 and alpha-lactalbumin 14 to break, thereby releasingbeta-lactoglobulin protein 12 with linkages 18 attached thereto. Thefree hydroxyl groups at the unattached ends of linkages 18 then reactwith the carboxyl groups of porphyrin IX to form ester-type bondstherewith. Thus attached, beta-lactoglobulin protein 12 places stress onthe prophyrin IX (applying a type of "pulling" action) therebyinhibiting prophyrin IX from accumulating so many water molecules. This,in turn, reduces the swelling, and gives the cell more time to degradethe prophyrin IX. Whatever the mechanism of multiprotein compound 10 intreating the symptoms of erythropoietic protoporphyria, it is clear thatmultiprotein compound 12 acts to alleviate the symptoms of swelling andsplitting of the skin caused by the accumulation of porphyrin IX.

As mentioned hereinabove, beta-lactoglobulin protein 12 and attachedlinkages 18 are believed to be the active ingredients of multiproteincompound 10 when used in a treatment for erythropoietic protoporphyria.In such a treatment, alpha-lactalbumin protein 14 serves to effectuateentry of multiprotein compound 10 into the cells, much in the samemanner as with the other treatments. The bacitracin proteins 16 act tostabilize the multiprotein compound structure 10 and to increase thehydrolyzing activity of alpha-lactalbumin protein 14.

The following components listed in Table V below and examples discussedhereinafter are given by way of general instruction to enable those ofordinary skill in the art to make multiprotein compounds within thescope of the present invention which may be used in the treatment oferythropoietic protoporphyria.

                  TABLE V                                                         ______________________________________                                                           Weight % of Compound                                       Component          (preferred range)                                          ______________________________________                                        beta-lactoglobulin 40-60%                                                     alpha-lactalbumin  10-20%                                                     fatty acids        15-31%                                                     zinc bacitracin    12-20%                                                     selenium (either as Se° or SeS)                                                           0.5-0.7%                                                   lanolin U.S.P.      7-20%                                                     petrolatum U.S.P.   1-10%                                                     glycerol           0-5%                                                       tartaric acid      0-3%                                                       benzoic acid       0-2%                                                       ethanol            0.5-1.5%                                                   ______________________________________                                    

The components listed above are combined in the same manner as outlinedin Example 1. It should be noted that although preferred ranges aregiven for alpha-lactalbumin, zinc bacitracin, selenium, petrolatum,glycerol, tartaric acid, benzoic acid, and ethanol, these components arepurely optional when making a multiprotein compound within the scope ofthe present invention for the treatment of erythropoieticprotoporphyria. It should be further noted that the fatty acids andlanolin can be used either in combination or alone to make multiproteincompounds within the scope of the present invention for the treatment oferythropoietic protoporphyria. Thus, where fatty acids are used alone,lanolin becomes an "optional" component, and conversely, where lanolinis used alone, the fatty acids become an "optional" component.

EXAMPLE 10

A multiprotein compound within the scope of the present invention whichhas been used in the treatment of erythropoietic protoporphyria was madeaccording to the procedure of Example 1, except that the components werecombined in the following amounts:

    ______________________________________                                        Compound             Amount (grams)                                           ______________________________________                                        beta-lactoglobulin   53.5     g.                                              alpha-lactalbumin    13.5     g.                                              fatty acid           8        g.                                              zinc bacitracin      11.5     g.                                              selenium monosulfide 0.7      g.                                              lanolin U.S.P. (anhydrous)                                                                         7        g.                                              petrolatum U.S.P.    3        g.                                              glycerol             1        g.                                              tartaric acid        1        g.                                              benzoic acid         1        g.                                              ethanol              0.5      g.                                              ______________________________________                                    

In this example, the fatty acid used was stearic acid (8 grams).

EXAMPLE 11

Another compound within the scope of the present invention useful in thetreatment of erythropoietic protoporphyria was made by combining thefollowing components in the indicated amounts:

    ______________________________________                                        Compound       Amount (grams)                                                 ______________________________________                                        beta-lactoglobulin                                                                           57 g.                                                          lanolin U.S.P.  7 g.                                                          linoleic acid  26 g.                                                          glycerol       10 g.                                                          ______________________________________                                    

These components were combined according to the following procedure: afirst fraction was prepared by mixing the lanolin with the glycerol andby heating the mixture to about 40° C. In a separate receptacle, asecond fraction was prepared by mixing the linoleic acid with about 1.7grams of a 30% sodium carbonate buffer solution, thereby bringing the pHto about 5.5. The second fraction was allowed to react for about 2.5hours at a temperature of about 24° C. while mixing thoroughly.

The components of fractions one and two were then combined and the pHwas adjusted to about 5.5 by adding an additional 0.3 grams of thebuffer solution. The resulting mixture was allowed to cool to about 25°C. and the beta-lactoglobulin was added to the mixture. The pH of themixture was again adjusted to about 5.5 by adding an additional 0.1grams of the buffer solution. This mixture was allowed to react for aperiod of about 2.5 hours, thereby producing a compound within the scopeof the present invention suitable for the treatment of erythropoieticprotoporphyria.

In treating erythropoietic protoporphyria, a compound such as that inExample 10 or 11 is generally applied topically in daily dosages ofabout 0.001-0.2 g/cm² of skin treated. The presently preferred dailydosage is about 0.08-0.2 g/cm² of skin treated.

One individual has been treated for erythropoietic protoporphyria withthe preferred compound of Example 10. This individual had beenpreviously treated unsuccessfully with X-rays and cortisone treatments.After receiving the erythropoietic protoporphyria treatment of thepresent invention for two days, the individual showed substantialsymptom relief. In particular, the swollen and split hands of theindividual were healed. Significantly, the disease has not recurredsince the termination of treatments.

D. Scar Tissue and Wounds

It is believed that most, if not all, of the components of themultiprotein compounds of the present invention act as activeingredients in treating scar tissue and in promoting wound healing.Basically, the process of tissue regeneration requires the presence ofphospholipids, sterols, and proteins. The basic building blocks of eachof these components are present in the structure of the multiproteincompounds of the present invention.

For example, proteins 12, 14, and 16 are degraded by the body into aminoacids which can subsequently be used to manufacture the necessaryproteins for tissue regeneration. Upon degradation of the multiproteincompounds, linkages 32 are converted into steroid alcohols which are thebasic building blocks for the sterols needed for tissue regeneration.Finally, upon degradation of multiprotein compounds, organic linkages41-44 are converted into fatty acids which are the basic building blocksof the phospholipids needed for tissue regeneration.

Thus, it will be appreciated that the multiprotein compounds of thepresent invention supplies most, if not all, of the raw materialsnecessary to promote wound healing and tissue regeneration. Moreover,the bacitracin proteins 16 of the multiprotein compounds provideanti-bacterial activity necessary in wound healing and tissueregeneration.

Finally, it is believed that multiprotein compound 10 acts to promotethe actual tissue regeneration mechanisms of the body. Although theprecise mechanism of tissue regeneration is not completely understood,it is believed that upon introduction of the multiprotein compounds intothe body, the body utilizes enzymes to break up the compounds; theseenzymes are the same enzymes involved in tissue regeneration mechanisms.Thus, it is postulated that the very introduction of the multiproteincompounds into the body attracts the necessary enzymes present in thebody which are responsible for tissue regeneration.

These three characteristics of multiprotein compound 10, i.e., (1)providing anti-bacterial activity, (2) providing a source of most, ifnot all, of the components needed for tissue regeneration, and (3)providing a means for actually promoting the tissue regenerationmechanisms of the body, combine to make the application of themultiprotein compounds an effective treatment for scar tissue and forpromoting wound healing and tissue regeneration.

The following components listed in Table VI below and example discussedhereinafter are given by way of general instruction to enable those ofordinary skill in the art to make multiprotein compounds within thescope of the present invention which may be used in the treatment ofscar tissue and wounds.

                  TABLE VI                                                        ______________________________________                                                           Weight % of Compound                                       Component          (preferred range)                                          ______________________________________                                        acetylglucosamine  2-4%                                                       beta-lactoglobulin 50-60%                                                     alpha-lactalbumin  10-20%                                                     lanolin U.S.P.      7-15%                                                     zinc bacitracin    12-20%                                                     selenium (either as Se° or SeS)                                                           0.5-0.7%                                                   petrolatum U.S.P.   5-10%                                                     fatty acids, cysteine, & alanine                                                                 15-31%                                                     glycerol            1-10%                                                     ethanol            0.5-1.5%                                                   ______________________________________                                    

The components listed above are combined in the same manner as outlinedin Example 1, with the exception that certain of the components ofExample 1 are omitted. It should be noted that although preferred rangesare given for acetylglucosamine, selenium, petrolatum U.S.P., glycerol,ethanol, cysteine, and alanine, these components are purely optionalwhen making a multiprotein compound within the scope of the presentinvention for the treatment of scar tissue and wounds.

The acetylglucosamine, cysteine, and alanine are mixed with the fattyacids of the second fraction in the procedure of Example 1. Moreover,sialic acid or neuraminic acid may be substituted for acetylglucosamine.

EXAMPLE 12

A multiprotein compound within the scope of the present invention usefulfor the treatment of scar tissue and for promoting wound healing hasbeen made by combining the following components in the indicatedamounts:

    ______________________________________                                        Component            Amount (grams)                                           ______________________________________                                        acetylglucosamine    4        g.                                              beta-lactoglobulin   44       g.                                              alpha-lactalbumin    11       g.                                              lanolin U.S.P. (anhydrous)                                                                         8        g.                                              zinc bacitracin      14.4     g.                                              selenium monosulfide 0.7      g.                                              petrolatum U.S.P.    5        g.                                              fatty acids          6.5      g.                                              cysteine             3        g.                                              alanine              2.0      g.                                              glycerol             1        g.                                              ethanol              0.5      g.                                              ______________________________________                                    

In this example, the fatty acids used were oleic acid (2 grams), elaidicacid (1 gram), palmitic acid (1.5 grams), and stearic acid (2.0 grams).From the foregoing, it will be recognized that a few additionalcomponents are included in this example of a multiprotein compound fortreating scar tissue and for promoting wound healing. It should be notedthat benzoic and tartaric acid preservatives may also be used inconjunction with the foregoing components. Moreover, since a commonsource for the beta-lactoglobulin and alpha-lactalbumin is hydrolyzedmilk protein, it may also be desirable to include other components ofthe hydrolyzed milk protein which have been found to have a beneficialeffect towards wound healing, e.g., acetylneuraminic acid, orthosialicacid, parasialic acid, glycolneuraminic acid, glycolsialic acid, andacetylsialic acid.

The foregoing components were combined as follows: A first fraction wasprepared by mixing the petrolatum U.S.P. with the lanolin U.S.P., andthe mixture was heated to about 35° C. Next, the ethanol was blendedinto the mixture while maintaining the temperature at about 35° C. Asecond fraction was prepared by mixing the fatty acids, cysteine,alanine, and acetylglucosamine (the tartaric acid and benzoic acidpreservatives would be added here if desired) together in a separatereceptacle at a temperature of about 22° C. A buffer solution of 25%potassium bicarbonate was added to the second fraction to adjust the pHto about 5.5. The second fraction was continually mixed for about 2.5hours until fully reacted and well blended. The second and firstfractions were then mixed together and cooled to about 30° C. and the pHwas again adjusted to about 5.5 by adding an additional 0.3 grams of thepotassium bicarbonate buffer solution. Finally, the zinc bacitracin andselenium monosulfide were blended into the mixture and the mixture wasslowly cooled to about 22° C. At this temperature, thebeta-lactoglobulin and alpha-lactalbumin were blended into the mixture.Subsequently, the pH was again adjusted by adding 0.1 grams of thepotassium bicarbonate buffer solution to maintain the pH at about 5.5.

Multiprotein compound 10 is generally applied topically when used totreat scar tissue and to promote wound healing. The daily dosage of suchapplications should be within the range of about 0.001-0.2 grams persquare centimeter (g/cm²). The presently preferred daily dosage is about0.08-0.2 g/cm², being administered in two daily applications of 0.04-0.1g/cm² each.

While additional studies are continuing, the only experimental resultsavailable for the application of the multiprotein compound of thepresent invention for treating scar tissue and for promoting woundhealing are those results reported above with regard to psoriasis. Sinceskin afflicted with psoriasis is generally characterized by what may betermed as "wounds," the experimental results obtained in the psoriasistreatments are also applicable to wound healing.

3. Additional Examples of Compounds of the Present Invention

Numerous other multiprotein compounds within the scope of the presentinvention have been made. Two hundred forthy-eight of these examples arereported in tabular form in Table VII below as Examples 13-260. In eachof these examples, the amount of the components used is reported inTable VII.

It is important to note that, in actuality, each of Examples 13-260reported in Table VII represents four separate compounds made; eachexample of Table VII has been carried out using bacitracin, zincbacitracin, calcium bacitracin, and magnesium bacitracin (thesebacitracin components being referred to generically as "bacitracin" inTable VII).

The multiprotein compounds reported in Table VII were made according tothe procedure of Example 1, with the exception that when alcohols andoils were added, they were added to the lanolin of the first fraction inthe procedure of Example 1. (The oils employed are esters which providealcohols and/or fatty acids upon hydrolysis.) The fatty acids, ofcourse, were added to the second fraction of the procedure of Example 1.It should be noted that in the examples where selenium is employed, theselenium was introduced as selenium monosulfide, except for Examples36-38, 60, 82, and 176 wherein selenium alone was used. However, foreach of the examples of Table VII where selenium sulfide was used, thegram quantities listed for "selenium" represent the gram weight of theselenium only, not the actual weight of selenium sulfide which wasadded. To convert these figures to gram weights of selenium sulfide,well-known conversion factors could be employed.

In order to better understood where each component was added in theprocedure of Example 1, the following categories are given as an aid indetermining which of the components listed in Table VII are categorizedas alcohols, oils, and fatty acids.

Alcohols: adenosine; B-caroten-3-ol; choline; colchiceine; cortisone;decyl-B-caroten-3-ol; pentyl-B-caroten-3-ol; picrotoxinin; sitosterol;stigmasterol; tocopherol.

Oils: coconut oil; corn oil; cottonseed oil; mineral oil; olive oil;palm oil; peanut oil; rice oil; safflower oil; sesame oil; soybean oil;sunflower oil; vegetable oil; wheatgerm oil.

Fatty Acids: acetylgluconic acid; acetylglucosamine; amino acids;aminobenzoic acid; aminolevulinic acid; arachidic acid; arachidonicacid; ascorbic acid; 1,3 dihydroxybenzoic acid; 2,5 dihydroxybenzoicacid; dodecanoic acid; citric acid; eicosanoic acid; eicosatrienoicacid; elaidic acid; folic acid; gluconic acid; linoleic acid; linolenicacid; meso-tartaric acid; myristic acid; nicotinic acid; oleic acid;palmitic acid; stearic acid; succinic acid; sulfamic acid; sulfanilicacid; thiophene-3-carboxylic acid; triacontanoic acid; undecanoic acid.

According to the procedure of Example 1, the alcohols and oils wereadded to the first fraction, and the fatty acids were added to thesecond fraction of that example.

    TABLE VII      COMPONENTS (GRAMS)       EXAMPLE NO.  13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29       Lactoglobulin 50 52 45 40 40 60 40 42 43 55 47 43.5 46 41 41.5 44 59     Lactalbumin 15 17 14 10 10  15 10 13  13 15 14.5 11 1.5 20 Bacitracin     11.5 11.5 11.5  24 19 12.3  22 11.5 15.4 13 12.5 Selenium   .5 .5 .5  1     1 .7  1 .5 .6 .5 .5 Petrolatum U.S.P.   5  3   4 3.3 7  3.5  2 5 Ethanol     .5  .5   1  .6 .7 .8    .9   1 Lanolin U.S.P. 12 15 18 14 7 20 7 12 10     20 8 13 12.5 20 7 7.5 18 Gylcerol 5 4  3 2  5 6 2.2  1 3.5 .5 .6 Benzoic     Acid 4 4  1     .3     1 Tartaric Acid 2 2  1     .5 Citric Acid 1.5     Ascorbic Acid 2 Folic Acid    2 1    1.5  .5 Choline    1 1    .5     Acetylgluconic Acid   3 3 Picrotoxinin         1 Gluconic Acid Aminoleuul     inic Acid 1   1     .5 Succinic Acid         .2  .3 Tryptophan    1     Nicotinic Acid         1  .5 Sulfanilic Acid         .5 Sulfamic Acid     1 Cortisone 1   1  2           1 Colchiceine  1  1     .5  .2     .1     Aminobenzoic Acid    1       .5 Sitosterol      5 4     1   3.4 Stigmaste     rol        .4   .5 Oleic Acid  1   2       .5 Stearic Acid  2 2 1     .2      10 Arachidic Acid     1 Arachidonic Acid  1   1  2          21     Elaidic Acid     1    .3     5  5 Linoleic Acid     2 10 2 5    8    5     Linolenic Acid    1       .5   1  5 Coconut Oil 6 1 3.5 5 14 2   7 7 5     1.5 4 23       EXAMPLE NO.  30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48     49 50 51       Lactoglobulin 44 47 53 51 56 60 42 45 47.5 40 41 42 43 44 45 60 58     58.5 50.5 57.5 56 54 Lactalbumin 20 15     13 13 14 10 12 13 12 11 15     Bacitracin       12 13 11.5 24 22 23 20 21 19.3 Selenium       .5 .5 .5     1 1 1 1 1 .7 Petrolatum U.S.P.       4 3.5 2 1 2 4 3.5 5 6 2.5 2 1 3 4     Ethanol .3   .5 .4 .3 .8  1 .5   1 1.5 1       .5 Lanolin U.S.P. 7.2 7     10 11 7.3 8 7.3 1.5 13.5 8.2 10 7.1 7.5 7.2 8 13.2 8 9 8.5 11 1.5 9.5     Glycerol 4.5 4      1 2   1.5 1 .9  3.3 4.5 5 6 7 Benzoic Acid    1.5 1     .5     .5     4 1  1.5 2.5 1 3.7 Tartaric Acid  1   1.5 1      .5 1   3     2  2.5 1.5 2 .3 Oleic Acid 4   2       1     5 2 2.5 3.5 4.5 15 12     Undecanoic Acid 1                .5 1 1.5 2 Eicosanoic Acid 1  5     .4 Dodecanoic Acid 1  1 Palmitic Acid 1        1.5  .5        10 Stearic     Acid 1  10     10 .5 11         13  15.5 Arachidic Acid Arachidonic Acid     5          1 Triacontanoic Acid 1          .5       1 Linoleic Acid          .5       2.5 Linolenic Acid 9                 .5 Palm Oil       2.4      6 Vegetable Oil             10   4 2 Coconut Oil   5  33.8   3.5  4.3 6        5 5 5 18    20 Safflower Oil  26 10 34        7.5 Cottonseed Oil   5           2      15 Sunflower Oil   1           8.8      10       EXAMPLE NO.  52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70     71 72 73 74 75 76 77 78 79 80 81       Lactoglobulin 43.5 46 47 48 49.5 42 41 40 59 58.5 57 53 54 55.5 56     54.5 52 42.5 46.5 50 58 56 41 42 42.6 43 44 50 51.5 52 Lactalbumin 20 18     17 15.5 13.5 19 17.5 14.5 10.5 17.5 18 19 18.3 18.2 12 12.5 13 15 17.5     10 10 10 10 11 12 13 13 10 10 10 Bacitracin         12           19.3     19.3 2.3 24 22 19.7 18 20 15.3 19 18 Selenium         .5           .7 .7     .7 1 1 .7 1 1 .7 1 1 Petrolatum U.S.P.                        2 6 3 5 1     .5 Ethanol .5 1 .7    .5 .6                .5 Lanolin U.S.P. 13 12 10 8     8 7.5 8 13 7.5 7 7 7 7 7 7 8 9 10 7.5 7 7 7 7 7 7 7 7 8 7 8 Glycerol 1 1     1 .5   1.5                5 4.5 .5 1 1.5 1 1.5 Benzoic Acid 2    1.5     1  .5  .5              .5  .5 Tartaric Acid .5 1 1 1     .5 1         1 1  1 Oleic Acid 3  1 2 1  1  5    .5  .3 2  1 1     5 3.5 1  1     Eicosanoic Acid 10 5 .3  1.5  .5 .9     .6 .3  3 1  .5         1 2     Palmitic Acid .5 5 2  1 1.5 1.5 1  6   4   10 5  20     1 1   1 Stearic     Acid 15 1 5 10  10 .5 5.5  5   5 1  10 1 1.5 2     1 1   1 5 4 Arachidoni     c Acid   1    3      2 1   1 5      1 2   1 Linoleic Acid   3 5  6 11     2.5  2 1  10 1 5 5 13    1 2 10  4 5 2 Palm Oil  1 1  5 4 4      2 2   1     10      1      5 Vegetable Oil  2 10 10    9.5     2 4 3   11 10     2 Coconut Oil  2   10  5 5   15  2    4      6 Safflower Oil  4   4 10 5       5    10   1    5 6 6    7 Cottonseed Oil     5       21   1.2 Sunflower      Oil         4      .5             5 B-caroten-3-ol 1 1      10     11   EXAMPLE NO.  82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99     100 101 102 103 104 105 106 107 108 109       Lactoglobulin 41 41 41 41 41 42 42 42 42 43 43 43 43 43 45 45 45 45 46     46 46 46 47 47 58 57 56 55 Lactalbumin 20 19 18 17 16 20 19 18 17 16 16     15 18 19 15 14 13 12 11 12 13 14 13 12 10 11 12 15 Bacitracin 11.5 12     11.5 12.4 11.5 11.5 11.4   11.5 11.5 11.5 11.5             11.5 12.3     Selenium .5 .5 .5 .6 .5 .5 .6   .5 .5 .5 .5             .5 .7 Petrolatum     U.S.P.  1 1 1 2 2 2  1 1 1 1  1 2   3  1  2  1  3 Ethanol        1     1           1 Lanolin U.S.P. 15 15 14 13 12 7 7.5 8 9 15 10 10 10 10 7 8 7 8 9     10 11 7 7 8 7 7 7 7 Glycerol 2  5 10 1 7 2.5 1 1  1 4 1    1 7  4  1 2 1     Benzoic Acid 3 5   3.5  5 5 5  2 5 5 2   4 5 Tartaric Acid  1   .5          .5  4 5 Oleic Acid   1  1   10 10 10 7  9 5   4.5   2 Eicosanoic     Acid     1         1      2 Palmitic Acid   1        1 5  1 Stearic Acid     2.5  1  1   15 15 3 2 5  13     5  15 30 31 31 25 Arachidonic Acid   1                 1 Linoleic Acid 1.5    1      5 Palm Oil 3     10 Vegetable Oil   5                15 Coconut Oil  1    10 10 Safflower     Oil  1 Sesame Oil  1               24 15 6 3 Cottonseed Oil  2 Sunflower     Oil  5  5           10      15     10 12 23 B-caroten-3-ol     1      9 pentyl-B-caroten-ol     1          5 5  1 2 1 decyl-B-caroten-3-ol      1          5 Tocopherol     5        1 5 2  1 3 2 1       EXAMPLE NO.  110 111 112 113 114 115 116 117 118 119 120 121 122 123     124 125 126 127       Lactoglobulin 55 56 57 58 59 60 54 53 52 40 41 42 43 44 40 4142 42     Lactalbumin          10 11 10 11 12 1.5 10 11 10 Bacitracin     11.3 11.5  24 23 22 21 Selenium            .7 .5  1 1 1 1 Pertrolatum     U.S.P.          1 2 2.5 3 3  1  1 Ethanol (40%) 1 1.5   .5 .6 .7 .9  1 1     1 1 Lanolin U.S.P. 7 7.5 7.6 8 10 8.5 7.3 7.1 13 15 8.6 9 9.5 13.28 8.4     8.5 9 Gylcerol          4 5 6 7 8 10 9 8 7 Benzoic Acid .5  1 2 3 4 5     1   2  .5  1 2.3 Tartaric Acid 1         .5 2 3 1  1  2.2 3.2 Oleic Acid       1       1.5  4.5 .5 5.3 5 6.5 Palmitic Acid   1.1       2  10 5 .5     4.3 Stearic Acid   29       15        3.5 Arachidonic Acid     3 Palm Oil Coconut Oil    29.6 Safflower Oil Sesame Oil Cottonseed Oil               5 Sunflower Oil  12 Tocopherol .1 .2 .1 .1 .1 .1 .5 .6 .7     10 Soybean Oil Olive Oil 1 1 1 1 1 1 1 1 1 Peanut Oil      35 Rice Oil         29    10 Corn Oil        35   10 Wheatgerm Oil 1 1.1 1.2 1.3 1.4 1.5     1.6 1.7 1.8  9 Myristic Oil 22.4 2.7     .9 .7 21.5  .4       EXAMPLE NO.  128 129 130 131 132 133 134 135 136 137 138 139 140 141     142 143 144 145       Lactoglobulin 43 43 44 45 46 47 48 40 41 42 42 41 43 43.5 44 50 55 60     Lactalbumin 11 12 13 10 11 12 13 11 12 11 10 13 14 15 10 1010 10     Bacitracin 19 18 20 19.8 17.8 19 11.4 11.4 12.4 11.8 13.5 14.5 13 12.4     13.5 14.4 11.5 11.5 Selenium 1 1 1 .7 .7 1 .6 .6 .6 .7 .5 .5 .5 .6 .5 .6     .5 .6 Petrolatum U.S.P.  1 1   1  2.5 1.5     1 Ethanol (40%)        1     1.2 1.3 1.4 Lanolin U.S.P. 0.5 10 1.5 11 11.5 12 12.5 13 14 15 16 17 18     1920 10 10 11 Gylcerol 6 5 4.5 8.5 7.3    1 2 3 4 5 6 5 5.5 Benzoic Acid      1     1  1  1 Tartaric Acid  2     1.2  1.5  1.2 1.3 1.4 1.5 1.6 Oleic     Acid .5 5   2.7  2.3 .5 .8 1.2  .7 1.1 .1 .4 .5 3 1 Palmitic Acid 2 2      1 1 1 1  1.5  .1 .1 .5 3 1 Stearic Acid 2     8  1 1 1  .5 .2 .1 .1 .5     3 1 Arachidonic Acid 2      1 1 1 1  .5 .2 .1 .1 .5 3 1 Palm Oil 2     1 1 1 1 .5 .5 .2 .1 .1 .5 1 1 Coconut Oil   6    1 1 1 1 .3 .5 .2 .1 .1     .5  1 Safflower Oil    5   1 1 1 1 1 .5 .2 .1 .1 .5  .1 Sesame Oil     1 1 1 1 .5 1 .2 .1 .2 .5  .1 Cottonseed Oil       1 1 1 1 .5 1 .2 .1 .2     1.5  .1 Sunflower Oil       1 1 1 1 .5  .2 .1 .1 1.5  .1 Tocopherol       1 1 1 .5  .2 1 1.5  .1 Soybean Oil       1 1 1 1 .5  .2  1 1.5  .1     Olive Oil        1 1 1 .5  .5  1 1.5  .1 Peanut Oil        1 1 1 2  .5     1 1.5  .1 Rice Oil        1  1 2 1    1.5  .1 Corn Oil        1  1 2     1.5  .1 Wheatgerm Oil     3   4   2  1   1.5  .1 Myristic Acid        1     1.1 1.1     3       EXAMPLE NO.  146 147 148 149 150 151 152 153 154 155 156 157 158 159     160 161       Lactoglobulin 4.5 41.5 42.5 43.5 44 44.5 46 47 48 49 50 51 41 42 43 44     Lactalbumin 10 1.5 11 11.5 12 12.5 1.7 11.3 12.3 12 10 10 1.21.4 1.6 11     Bacitracin 24 23.5 23 22 21.5 21 20 21 22 2.4 19 15.2 24 23.6 23.6 22     Selenium 1 1 1 1 1 1 1 .7 .7 .9 1 .8 .8 1 .8 1 Petrolatum U.S.P.  1  1     1  1  2 Ethanol (70%) .5 .5 .5   1 .3 2 Lanolin U.S.P.* 13 12 11 10 9 8     7 7 7.2 7.3 7 7 8.2 8.4 8 7.5 Glycerol (5% H.sub.2 O)  1 .5 .7 .8 .9 1     .2 .4 3  1 5 5 4 3 Benzioc Acid .3 .2 .4 .5         1 3 2 1 Tartaric     Acid .2 .3 .6 .5         3 1 2 1 Oleic Acid .5 8.5 .5 9 .7 1.1 1 .8 .4     .4    .6  .5 Palmitic Acid   9 .3 1        .8 Stearic Acid 10    10     3 5 6 Eicosatrienoic Acid              5 Arachidonic Acid Palm Oil     4         6 Coconut Oil      5 13 Safflower Oil                9 Sesame     Oil        9 Cottonseed Oil            10 Sunflower Oil Tocopherol     Soybean Oil         9 5 Olive Oil Peanut Oil Rice Oil Wheatgerm Oil     Myristic Acid           10       EXAMPLE NO.  162 163 164 165 166 167 168 169 170 171 172 173 174 175     176       Lactoglobulin 45 46 40 40 40 41 42 43 44 45 46 47 48 49 50 Lactalbumin     12.2 11.4 19 20 20 19 18 17 17.5 16.5 16 15.5 14.5 13.6 14.2 Bacitracin     21 19.8 22 11.5 11.8 12.5 13.4 14.5 13.3 12.5 11.5 11.5 12.5 13.4 13.1     Selenium 1 .8 1 .5 .7 .5 .6 .5 .7 .5 .5 .5 .5 .6 .7 Petrolatum U.S.P. 1     1  .5 1 1.5 2 2.5 3 2 1 .5 Ethanol (70%) Lanolin U.S.P.* 7 7 12 12.6     12.4 12 11.5 10 9.5 9 8.5 8 7 7 7 Glycerol (5% H.sub.2 O) 1 1.5 1.8 1 1     1 1 1 1.2 1.4 1.5 2 Benzoic Acid 1.5    .6         .4 Tartaric Acid 1.5       1 Oleic Acid .8 2.5 3.2 Palmitic Acid  10  .4 Stearic Acid    14     Eicosatrienoic Acid Arachidonic Acid             1 Palm Oil Coconut Oil                 14 Safflower Oil 8 Sesame Oil Cottonseed Oil Sunflower Oil               1 Tocopherol             1 2 1 Soybean Oil        1 .3 1.1     Olive Oil     12 13 12 11 11 11 11 14 Peanut Oil           3 Rice Oil              1 Wheatgerm Oil            .5   14 Myristic Acid     13   EXAMPLE NO.  177 178 179 180 181 182 183 184 185 186 187 188 189     190 191 192       Lactoglobulin 60 59 58 58 53 49 49 56 57 57 56 55 54 53 52 46 Lactalbum     in     20 20 19 18 17 16 15 16 17.5 20 19 18 Bacitracin     11.5 11.5     12.3 11.3 11.5 12.5 13.3 12 12 11.5 11.5 11.5 Selenium     .5  .7 .7 .5     .5 .7 .5 .5 .5 .5 .5 Petrolatum U.S.P.     .5   .5  .5 1 1  .5 1 1     Ethanol (80%) .5 1 1 1 1 1 1 1 1 1 1 2 2 2 1.5 1.2 Lanolin U.S.P.* 7 7 7     7 7 7 7.5 7 7 8 8.3 8.4 9 7.5 9 13 Glycerol (10% H.sub.2 O)     1 1.2     1.4 1.3 1 .5  1 .7 .8 1 1.1 Benzoic Acid  5  2 1     .5 .7  .8  1 1.5     Tartaric Acid   4 3 .4     1 .3  .2  1 1.2 Oleic Acid .5 3 1 1 .1 1 1.1     .1 .2 .5 .2 .1 .3  1 Palmitic Acid 22 20 30 3  .8 1 .1 .2 .5 .5 1 1  1     Stearic Acid 10 5  25  1 1 .1 .2 .5 .1 1 1  .1 Eicosatrienoic Acid     1 2 .1 .2 .5 .1 1 1  .1 Arachidonic Acid      1 2 .1 .2 .5 .1 1  .2 .1     Palm Oil      1 2 .1 .2  .1   1 .1 Coconut Oil**      1  .1 .2  .1   1     .1 Safflower Oil     4 .5  .1 .2  .1   1 Sesame Oil      .5  .1 .2  .5     1  1 Cottonseed Oil***        .1 .2  .4     1 Sunflower Oil        .1 .5      1.5     1 Soybean Oil        .1 .5       1 Olive Oil        1 .5 Peanut     Oil        1 .5 Rice Oil        1 .5 Wheatgerm Oil**         .5 Myristic     Acid       EXAMPLE NO.  193 194 195 196 197 198 199 200 201 202 203 204 205 206     207 208       Lactoglobulin 50 49 48 45 40 45 43 42 46 47 50 52 53 54 55 60 Lactalbum     in     12 12.5 13 12 14 15 12.5 13 14 15 16 12 Bacitracin     11.4 12.4     13.4 11.4 12.4 13.4 14.5 14 14.3 14.3 14.3 14.5 Selenium     .6 .6 .6 .6     .6 .6 .5 .5 .7 .7 .7 .5 Petrolatum U.S.P.     .5 .6 .7 .8 .9 1 1.1 1.2     1.3 1.4 1.5 Ethanol (80%) 1 .5 .7 .3 1 1 1 2.5 1.7 1.2   1 Lanolin     U.S.P.* 14 15 16 17 7.1 7.2 7.3 7.4 7.5 7.6 8 9 7 7 7 7 Glycerol (10%     H.sub.2 O) 1.2      3 2 2.5 4 2 2.2 2 2 2 2 Benzoic Acid       1 .3 .4     .2 .4 .1 .2 Tartaric Acid       1 1 1 .5 1 3.5 .5 Oleic Acid .8    .4 .7     1 1 1 .5 1 .5 .5 .6 .5 .1 Palmitic Acid 30 35    1 1 1 1 .5 1 1 .5 .5     .1 Stearic Acid 7 .5    1 1 1 1 .5 1 1 .5 .5  .1 Eicosatrienoic Acid     .3 .7  1 1 1 1 1 1 1 .5 .5  .1 Arachidonic Acid    2  1 1 1 1 1 2 1 .5     .5  .1 Palm Oil    35  2 1 1 1 1 2 1 .5 1  .5 Coconut Oil**    2.7 2 1 1     1 1 2 1 .5 1  1 Safflower Oil     .3 2 1 1 1 1  1 .5 1 Sesame Oil     5     2 1 1 1   1 .5  1 Cottonseed Oil***     5 2 1 1 1   1 .5  1 Sunflower     Oil     5 2 1 1 1   1 .5 Soybean Oil     5 2 1 1 1   1 .5  1 Olive Oil     35  4 2 1 1 1   1 Peanut Oil       1 1    1 Rice Oil       1 1    1    1     Wheatgerm Oil**       1 1        1 Myristic Acid        2       EXAMPLE NO.  209 210 211 212 213 214 215 216 217 218 219 220 221 222     223       Lactoglobulin****** 40 41 42 43 44 45 46 47 48 47 46 45 44 50 51     Lactalbumin****** 10 11 17 18 19 10 11.6 11.7 12 13 12 14 15 10 11     Bacitracin 24 23 22 21 22.7 19 14.3 15.2 16.2 17 18 19 18.2 11.5Selenium     1 1 1 1 .8 1 .7 .8 .8 1 1 1 .8 .5 Petrolatum U.S.P. 6 3.5 3     1 1 1 3      7 Ethanol (50%) 1 1 1 1      .5 .5   .2 Lanolin U.S.P.* 7.2 7.5 8 8.5 9     8 7.4 13.3 12 11 7 15 17 10 10 Gylcerol (15% H.sub.2 O) .5 2 1.5 1 1.2     2.5 3   1.2 1.3 1.4 1.5 1 Benzoic Acid*****  1 .5  1   3  .3 .2  .5 .8 1     Meso-Tartaric Acid .5 1 1 1 .5 1 2  1 1 Oleic Acid              1 10     Palmitic Acid             3  10 Stearic Acid               5 Eicosatrieno     ic Acid Arachidonic Acid Palm Oil**     1 Coconut Oil** Safflower Oil     Sesame Oil              5 Cottonseed Oil****    5       10 Sunflower Oil                4.6  1 Soybean Oil**         9 Olive Oil          7    1     Peanut Oil**    .5 .8 10 Rice Oil 8             1 Wheatgerm Oil** 1.8 8     3   3 15 8 Myristic Acid  .5    .5     1    2       EXAMPLE NO.  224 225 226 227 228 229 230 231 232 233 234 235 236 237     238       Lactoglobulin****** 52 53 54 54 55 56 56 57 58 59 60 45 50 55 51     Lactalbumin****** 12 13 14 15 10 11 10 10 1.5 12 13 12 11 12 11 Batcitrac     in     16.3    11.4 12 12.5 13 13.4 13.5 12.4 Selenium     .7    .6 .5     .5 .5 .6 .5 .6 Petrolatum U.S.P.    1 2 Ethanol (50%)     .9   1   .5     .7 Lanolin U.S.P.* 10 9 8 8 7 7 7 7 7 7 7 15 10 8 8 Gylcerol (15%     H.sub.2 O)       .3 1 1 Benzoic Acid***** 1 1    .3 .7 4 .5 .5  2 .9     Meso-Tartaric Acid    .5 .6 .7     1  .1 Oleic Acid     2 5  10     .3     Palmitic Acid     2 10  2 3 Stearic Acid  10   2 5  2 2 Eicosatrienoic     Acid       5 2 2 Arachidonic Acid  1     4  2 Palm Oil**  1     1  1     Coconut Oil**  1     1  1 Safflower Oil  1   1.5 2 1 Sesame Oil  1    3     1 Cottonseed Oil****  1  5   1 Sunflower Oil 5 1  4   1 Soybean Oil**  1     5 1   1 Olive Oil 5 1 5    1   9 5.5 Peanut Oil**  1 4    1     12 13     15 Rice Oil 5 4 10 10   1 4      11 Wheatgerm Oil**       1 Myristic     Acid 10   1.5   6     .5   2       EXAMPLE NO.  239 240 241 242 243 244 245 246 247 248 249 250 251 252     253 254 255 256 257 258 259 260       Lactoglobulin 60 55 50 45 40 41 43 45 47 49 51 53 54 55 57 59 60 58 56     54 52 50 Lactalbumin (anhydrous) 10 10 10 11 10 12 13 15 10 13 15 13.5     20 18 16 10 11 12 13 Bacitracin 16 19.2 15.2 16.2 24 17.2 16.2 15.7 19     20 20        11.5 12.3 11.8 13.5 Selenium 1 .8 .8 .8 1 .8 .8 .8 1 1 1         .5 .7 .7 .5 Petrolatum U.S.P. (heavy)   1 5   1           2   1     Petrolatum U.S.P. (medium)    4   1           2   1 Ethanol (50%)   1 1      1              1 Glycerol (50% H.sub.2 O)   1 3   1       4    .2   1     2,5 Dihydroxybenzoic Acid   1 1          1       .5 Para-Tartaric Acid     1 1          2 Oleic Acid   11 4  5           .5 Elaidic Acid     10      .5   10 Palmitic Acid .6    4           1 2 .5 Palm Oil*** .4     1           1 2 .3 Coconut Oil**** 5            26 20 16 1 2 Safflower     Oil  5      10       10 1 1 Sesame Oil      7          1   15 Cottonseed     Oil          7      1    14 Olive Oil**         10  6 3    1 Peanut     Oil**                1      13 Rice Oil**                1 Adenosine  1       2          1 1    1 2 Thiophene-3-Carboxylic Acid  1    1      1    1     2   .5 Lanolin U.S.P. (5% hydrous) 7 8 7 8 20 19 18 13.5 13 20 7 20 20     18 17 10 12 20 7 7.5 8 8     *hydrous     **hydrogenated     ***partially hydrogenated (30% by weight)     ****partially hydrogenated (35% by weight)     *****1,3 dihydroxybenzoic acid     ******anhydrous

From the foregoing, it will be appreciated that the present inventionprovides multiprotein compounds including beta-lactoglobulin,alpha-lactalbumin, and bacitracin which are useful and effective in thetreatment of such medical disorders as psoriasis, arthritis,erythropoietic protoporphyria, and scar tissue and wounds.

The present invention may be embodied in other specific forms withoutdeparting from its spirit or essential characteristics. The describedembodiments are to be considered in all respects only as illustrativeand not restrictive. The scope of the invention is, therefore, indicatedby the appended claims rather than by the foregoing description. Allchanges which come within the meaning and range of equivalency of theclaims are to be embraced within their scope.

What is claimed and desired to be secured by United States LettersPatent is:
 1. A chemical compound comprising:at least one molecule ofbacitracin having adjacent isoleucine and cysteine amino acid residues;and at least one selenium ion, each of said selenium ions beingsubstituted for a sulfur atom in a sulfide bond between the adjacentisoleucine and cysteine amino acid residues in a correspondingbacitracin molecule.
 2. A chemical compound as defined in claim 1wherein said bacitracin is supported by a chemical support structurecomprising at least one molecule of alpha-lactalbumin, saidalpha-lactalbumin being linked to said bacitracin by a plurality offirst organic linkages, each of said first organic linkages comprising ahydrocarbon chain having a length from about 8 to about 50 carbon atoms.3. A chemical compound as defined in claim 2 wherein said first organiclinkages are formed by reacting fatty acids with said alpha-lactalbuminand said bacitracin.
 4. A chemical compound as defined in claim 1wherein said bacitracin is supported by a chemical support structurecomprising at least one molecule of alpha-lactalbumin, saidalpha-lactalbumin being linked to said bacitracin by a plurality offirst organic linkages, each of said first organic linkages comprising ahydrocarbon chain having a length from about 14 to about 20 carbonatoms.
 5. A chemical compound as defined in claim 2 wherein the chemicalsupport structure further comprises at least one molecule ofbeta-lactoglobulin, said beta-lactoglobulin being linked to saidalpha-lactalbumin by a plurality of second organic linkages, each ofsaid second organic linkages comprising a hydrocarbon chain having alength from about 8 to about 50 carbon atoms.
 6. A chemical compound asdefined in claim 5 wherein said second organic linkages are formed byreacting alcohols with said beta-lactoglobulin and saidalpha-lactalbumin, said alcohols being selected from the groupconsisting of noncyclic aliphatic alcohols, steroid alcohols, andtriterpenoid alcohols.
 7. A chemical compound as defined in claim 2wherein the chemical support structure further comprises at least onemolecule of beta-lactoglobulin, said beta-lactoglobulin beig linked tosaid alpha-lactalbumin by a plurality of second organic linkages, eachof said second organic linkages comprising a hydrocarbon chain having alength from about 14 to about 20 carbon atoms.
 8. A chemical compound asdefined in claim 5 wherein said beta-lactoglobulin is further linked tosaid alpha-lactalbumin by one or more third organic linkages, said thirdorganic linkages being formed by reacting thioglycerol molecules withsaid beta-lactoglobulin and said alpha-lactalbumin.
 9. A chemicalcompound as defined in claim 1 further comprising at least one zinc ion,each of said zinc ions being associated with at least one bacitracinmolecule so as to form a salt therewith.
 10. A chemical compound asdefined in claim 1 further comprising at least one calcium ion, each ofsaid calcium ions being associated with at least one bacitracin moleculeso as to form a salt therewith.
 11. A chemical compound as defined inclaim 1 further comprising at least one magnesium ion, each of saidmagnesium ions being associated with at least one bacitracin molecule soas to form a salt therewith.
 12. A chemical compound comprising:at leastone molecule of beta-lactoglobulin; at least one molecule ofalpha-lactalbumin, said alpha-lactalbumin being linked to saidbeta-lactoglobulin by a plurality of first organic linkages, each ofsaid first organic linkages comprising a hydrocarbon chain having alength from about 8 to about 50 carbon atoms; at least one molecule ofbacitracin having adjacent isoleucine and cysteine amino acid residues,said bacitracin being linked to said alpha-lactalbumin by a plurality ofsecond organic linkages, each of said second organic linkages comprisinga hydrocarbon chain having a length from about 8 to about 50 carbonatoms; and at least one selenium ion, each of said selenium ions beingsubstituted for a sulfur atom in a sulfide bond between the adjacentisoleucine and cysteine amino acid residues in a correspondingbacitracin molecule.
 13. A chemical compound as defined in claim 12wherein each of said first organic linkages comprises a hydrocarbonchain having a length from about 14 to about 20 carbon atoms and whereineach of said second organic linkages comprises a hydrocarbon chainhaving a length from about 14 to about 20 carbon atoms.
 14. A chemicalcompound as defined in claim 13 wherein said first organic linkages areformed by reacting alcohols with said alpha-lactalbumin and saidbeta-lactoglobulin, said alcohols being selected from the groupconsisting of noncyclic aliphatic alcohols, steroid alcohols, andtriterpenoid alcohols.
 15. A chemical compound as defined in claim 14wherein said beta-lactoglobulin is further linked to saidalpha-lactalbumin by one or more third organic linkages, said thirdorganic linkages being formed by reacting thioglycerol molecules withsaid beta-lactoglobulin and said alpha-lactalbumin.
 16. A chemicalcompound as defined in claim 13 wherein said second organic linkages areformed by reacting fatty acids with said bacitracin and saidalpha-lactalbumin.
 17. A chemical compound as defined in claim 12further comprising at least one zinc ion, each of said zinc ions beingassociated with at least one bacitracin molecule so as to form a salttherewith.
 18. A chemical compound as defined in claim 12 furthercomprising at least one calcium ion, each of said calcium ions beingassociated with at least one bacitracin molecule so as to form a salttherewith.
 19. A chemical compound as defined in claim 12 furthercomprising at least one magnesium ion, each of said magnesium ions beingassociated with at least one bacitracin molecule so as to form a salttherewith.
 20. A chemical compound as defined in claim 12 wherein eachmolecule of the compound comprises one molecule of beta-lactoglobulin,two molecules of alpha-lactalbumin, eight molecules of bacitracin, andeight selenium ions.
 21. A chemical compound comprising:at least onemolecule of beta-lactoglobulin; at least one molecule ofalpha-lactalbumin; and a plurality of organic linkages linking saidbeta-lactoglobulin to said alpha-lactalbumin, each of said organiclinkages comprising a hydrocarbon chain having a length from about 8 toabout 50 carbon atoms.
 22. A chemical compound as defined in claim 21wherein said organic linkages are formed by reacting alcohols with saidbeta-lactoglobulin and said alpha-lactalbumin, said alcohols beingselected from the group consisting of noncyclic aliphatic alcohols,steroid alcohols, and triterpenoid alcohols.
 23. A chemical compound asdefined in claim 22 wherein said beta-lactoglobulin is further linked tosaid alpha-lactalbumin by one or more second organic linkages, saidsecond organic linkages being formed by reacting thioglycerol moleculeswith said beta-lactoglobulin and alpha-lactalbumin.
 24. A chemicalcompound as defined in claim 21 wherein each of said organic linkagescomprises a hydrocarbon chain having a length from about 14 to about 20carbon atoms.
 25. A chemical compound comprising:at least one moleculeof beta-lactoglobulin; and a plurality of organic molecules attached tosaid beta-lactoglobulin, each of said organic molecules comprising ahydrocarbon chain having a length from about 8 to about 50 carbon atoms.26. A chemical compound as defined in claim 25 wherein said organicmolecules attached to said beta-lactoglobulin comprise alcohols whichare reacted with said beta-lactoglobulin, said alcohols being selectedfrom the group consisting of noncyclic aliphatic alcohols, steroidalcohols, and triterpenoid alcohols.
 27. A chemical compound as definedin claim 25 wherein each of said organic molecules comprises ahydrocarbon chain having a length from about 14 to about 20 carbonatoms.
 28. A chemical compound comprising:one molecule ofbeta-lactoglobulin; two molecules of alpha-lactalbumin; a plurality offirst organic linkages linking said molecule of beta-lactoglobulin tosaid molecules of alpha-lactalbumin, said first organic linkages beingformed by reacting alcohols with said molecule of beta-lactoglobulin andsaid molecules of alpha-lactalbumin, said alcohols being selected fromthe group consisting of noncyclic aliphatic alcohols, steroid alcohols,and triterpenoid alcohols, each of said alcohols comprising ahydrocarbon chain having a length from about 14 to about 20 carbonatoms; eight molecules of bacitracin, each of said bacitracin moleculeshaving adjacent isoleucine and cysteine amino acid residues; a pluralityof second organic linkages linking said molecules of alpha-lactalbuminto said molecules of bacitracin, said second organic linkages beingformed by reacting fatty acids with said molecules of alpha-lactalbuminand said molecules of bacitracin, each of said fatty acids comprising ahydrocarbon chain having a length from about 14 to about 20 carbonatoms; and eight selenium ions, each of said selenium ions beingsubstituted for a sulfur atom in a sulfide bond between the adjacentisoleucine and cysteine amino acid residues in a corresponding one ofsaid bacitracin molecules.
 29. A chemical compound as defined in claim28 further comprising four zinc ions, each of said zinc ions beingassociated with two of said bacitracin molecules so as to form a salttherewith.